Load packages and prep data

Load packages

source('9. load_pkgs_BcellAnalysis.R')
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clusterProfiler v4.12.6 Learn more at https://yulab-smu.top/contribution-knowledge-mining/

Please cite:

Guangchuang Yu, Li-Gen Wang, Yanyan Han and Qing-Yu He. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS: A
Journal of Integrative Biology. 2012, 16(5):284-287

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loadfonts('pdf')
theme_set(theme_classic())
my_theme <- theme(
  text = element_text(family = 'ArialMT'),
  axis.line = element_line(linewidth = 1),
  axis.ticks = element_line(linewidth = 0.5),
  axis.title = element_text(size = 10),
  axis.text = element_text(size = 8),
  legend.title = element_text(size = 8),
  legend.text = element_text(size = 8)
)
theme_update(
  text = element_text(family = 'ArialMT'),
  axis.line = element_line(linewidth = 1),
  axis.ticks = element_line(linewidth = 0.5),
  axis.title = element_text(size = 10),
  axis.text = element_text(size = 8),
  legend.title = element_text(size = 8),
  legend.text = element_text(size = 8))
  

Define custom functions

Spatial analysis functions

Create adjacency matrix

Function that creates an adjacency matrix by querying each cell for the cell types of each target cell within a certian distance X, then sums across each cell type.


# Define function
make_adj_mat <- function(
  # output of dist function  
  dist_obj, 
  # named list of cell names and cell types
  annot_list,
  # distance
  distX,
  # collapse query cells? (i.e. columns)
  collapse_query = T) {  
  
  ## retrieve matrix object from dist object
  dmat <-as.matrix(dist_obj)
  
  ## iterate through each query cell
  tmpmat <- sapply(colnames(dmat), function(cellid) {
    
    ### obtain all target cells within distX distance
    cell <- dmat[,cellid]
    cell_fil <- cell[which((cell < distX) & (cell != 0))]
    ### get the cell type of each cell and count using the annot dataframe
    out <- t(as.matrix(table(annot_list[names(cell_fil)])))
    row.names(out) <- cellid
    return(out)
  })
  
  ## put all cells together
  tmpmat <- rbind.fill.matrix(tmpmat)
  row.names(tmpmat) <- colnames(dmat)
  ## add clust to each query cell
  tmpmat <- as.data.frame(tmpmat)
  tmpmat$celltype <- annot_list[row.names(tmpmat)]
  
  ## collapse all query cells into clust as well
  if(collapse_query){
  
  outmat <- tmpmat %>% group_by(celltype) %>%
  summarise(across(everything(), ~ sum(., na.rm=T)))
  rnames <- outmat$celltype # make rownames the cell type 
  outmat <- as.matrix(outmat[,which(colnames(outmat) !='celltype')]) # remove celltype column
  row.names(outmat) <- rnames
  outmat <- outmat[colnames(outmat),] # make rownames and colnames the same order
  } else {
  outmat <- tmpmat
  }
  
  ## return the final dataframe
  return(outmat)
  
  }

Get hypergeo parameters

Going to use a hypergeometric distribution of edges ab, where a = celltype 1 (ct1), b = celltype2 (ct2), and: * x = observed number of times ab is seen in the data * m = total number of possible edges that include ab * if a != b: m = (Na * Nb) * if a == b: m = choose(Na,2) * n = total number of possible edges that DON’T include ab: [ (((Nt*Nt)-Nt)/2) - m ] (cells can’t be their own edge; draw a dummy matrix to make sense of this formula) * k = number of edges in the dataset

Note that it’s ok to add these values together across cells from the same “group”

# Define function
adj_mat_to_hypergeo_params <- function(
    # adjacency matrix
    outmat,   
    # named vector of number of cells of each type in the dataset. Names must match adjacency matrix column and row names               
    nctypes)
  { 

    # ensure that all cell types are found in each of
    ## rownames outmat
    ## colnames outmat
    ## names of nctype
    if(any(row.names(outmat) != colnames(outmat))) {
      stop("Row names and column names of outmat do not match.")
    }
      
    if(!(all(row.names(outmat) %in% names(nctypes)) & all(names(nctypes) %in% row.names(outmat)))) {
      stop("Row names of outmat and names of nctype do not match.")
    }
    
  
    ## create output dataframe:
    ### determine unique combinations of cell types
    #### sort nctypes first to make sure that the combinations are made correctly
    out <- as.data.frame(combinations(n = length(names(nctypes)),
                                        r = 2,
                                        v = sort(names(nctypes)),
                                        repeats.allowed = T))
    colnames(out) <- c('ct1', 'ct2')
  
    ## calc total number of each cell type in dataset
    nt_cell <- sum(nctypes)
    nt_edge <- sum(outmat)/2
    
    ## for each cell in the adjacency matrix, define parameters of hypergeometric distribution
    ## if output = 'hyper_fit', then determine p values and expected number of edges given the params
    
    params <- t(apply(out, 1, function(r) {
        
        ### define ct1 and ct2
        ct1 = unlist(r['ct1'])
        ct2 = unlist(r['ct2'])
      
        ### define parameters of hypergeometric distribution
        x <- outmat[ct2, ct1]
        if(ct1==ct2) {
              m <- choose(nctypes[ct1], 2)} else {
              m <- nctypes[ct1] * nctypes[ct2]}
        n <- ((nt_cell * nt_cell) - nt_cell)/2 - m
        k <- nt_edge
        
        ### return parameters
        return(c(m, n, k, x))
          
        }))
    
    out <- cbind(out, params)
    colnames(out) <- c('ct1', 'ct2', 'm', 'n', 'k', 'x')   
    return(out)  
    }
    

Fit hypergeo parameters

This function fits the data to a hypergeometric distribution and calculates fold increased interactions over expected

# Define function
fit_hyper_geo <- function(
    # the number of observed interactions between two cell ty pes
    observed_edge_n,   
    # the expected hyperparameters for those two cell types
    expec_hyperparams
    ){ 
  
  
  ## calc the expected number of edges
  expec <-  n*K/N
  
  ## calc the fold increase of observed / expected
  foldincr <- observed_edge_n / expec
  
  ## calc the p value 
  pval <- phyper(q=x,
                 m=m,
                 k=k,
                 n=n,
                 lower.tail = T,
                 log.p = T)
          
  ## return the data
  out = list(expec, foldincr, pval)
  names(out) = c('null.expec.edges', 'fold.incr.over.null', 'p.val')
  return(out)
}
  
genemods_mle_findmarkers <- function(seurat_obj, # Seurat object
                                     rawdata = NULL, # sparse counts matrix, rows = genes, columns = cells
                                     mle_negm, # vector of mean negprobe counts per cell, see "insitutype" function
                                     mle_cohort, # dataframe of parameters used for fastCohorting, see "insitutype" function
                                     mle_nclust = NULL, # vector of length 2 specifying the minimum and maximum number of clusters for MLE cell to generate
                                     logfc_min = 0.5 # minimum log2fc required for genes to be designated as marker genes of a subcluster
                                     ) {
  
  
  # define raw data if undefined
  if(is.null(rawdata)) {
    rawdata <- seurat_obj@assays$nanostrRNA@counts
  }
  
  
  # define nclust if undefined
  if(is.null(mle_nclust)) {
    mle_nclust <- c(2, 
  ## the maximum number of clusters should either be the lesser of: (a) the number of genes or (b) the number of cells / 10, assuming that clusters on average should have at least 10 cells
                    min(c(nrow(raw), round(ncol(raw)/10))))
  }
  
  
  # Perform unsupervised cell clustering
    ## Cohort cells
    mle_coho <- fastCohorting(mat = mle_cohort,
                              gaussian_transform = TRUE)
    
    
    ## Cluster cells
    mle_unsup <- insitutype(counts = t(as.matrix(rawdata)),
                            neg = mle_ngem,
                            cohort = mle_coho,
                            n_clusts = mle_nclust,
                            reference_profiles = NULL) # NULL value runs unsupervised clustering
    
    
    ## Plot clusters
    mle_hm <- heatmap(sweep(mle_unsup$profiles,
                            1,
                            pmax(apply(mle_unsup$profiles, 1, max),
                                 .2),
                            "/"),
                      scale = "none",
                      main = "Subcluster Mean Expression Profiles")
    
    
    ## Add cluster data to Seurat object
    seurat_obj <- AddMetaData(seurat_obj, 
                              data.frame(mle_unsup$clust))
  
  
  # Run Marker Gene analysis
  Idents(object = seurat_obj) <- seurat_obj@meta.data$'mle_subclust' 

  mle_subclust_markers <- FindAllMarkers(seurat_obj,
                                         only.pos = TRUE,
                                         min.pct = 0.25)
  

  # Output
  out <- list()
  out$cell_cluster_heatmap <- mle_hm
  
  return(out)
  
}

 

Load data

set.seed(0)
load("processed_data/cleaneddata.RData") # scRNAseq data
load("processed_data/cannot with distances from gloms.RData") # glomerular distance information from Patrick
context <- readRDS('processed_data/context4.RDS')
names(context) <- colnames(raw)
contam <- readRDS('processed_data/toomuchcontam.RDS') # gene contamination calls by Patrick

Pre-process data

To remove genes that are “expressed” in cells due to poor segmentation, I will use Patrick’s contamination dataset: “contaminating transcripts from imperfect cell segmentation – e.g. if a B-cell is surrounded by PCT cells, then when we occasionally draw a cell boundary wrong we’ll place some PCT transcripts in a B-cell. So if any of your clusters are driven by genes typical of another cell type, suspect an artifact. For each cell type x gene, the attached matrix measures how much the gene comes from the appropriate cell type vs. from contamination – higher values mean more pure / less contaminated data. You can use this to check if any of your B-cell cluster marker genes are contaminants. For differential expression, I’m only considering genes with values above 0.2.”

Will use cotamstat.RDS to look at the contamination rates from the gene. We can look at each statistically significant gene

Define cell types and filter genes

Distribution of gene contamination scores


cd4_tcell_types <- c( "T CD4 memory",
                      "T CD4 naive",
                      "Treg")

cd8_tcell_types <- c( "T CD8 memory",
                      "T CD8 naive")

glomcell_types <- c("Podocyte",
                    "Glomerular.endothelium",
                    "Mesangial.cell",
                    "Parietal.epithelium")

vesslcell_types <- c("Vascular.pericyte",
                     "Peritubular.capillary.endothelium.1",
                     "Peritubular.capillary.endothelium.2",
                     "Ascending.vasa.recta.endothelium",
                     "Descending.vasa.recta.endothelium")

tubcell_types <- c("Connecting.tubule",
                   "PCT",
                   "Principal.cell",
                   "Type.A.intercalated.cell",
                   "Type.B.intercalated.cell",
                   "Pelvic.epithelium",
                   "Thick.ascending.limb.of.Loop.of.Henle",
                   "Indistinct.intercalated.cell",
                   "Transitional.urothelium",
                   "Epithelial.progenitor.cell")

innate_lymph <- c("NK")

interstcell_types <- c("Myofibroblast",
                       "Fibroblast")

# Define cell types
all_cell_types <- levels(as.factor(clust))

imm_cell_types <- c("B-cell",
                    "macrophage",
                    "mast",
                    "mDC",
                    "monocyte",
                    "neutrophil",
                    "NK",
                    "pDC",
                    "plasmablast",
                    "T CD4 memory",
                    "T CD4 naive",
                    "T CD8 memory",
                    "T CD8 naive",
                    "Treg")

b_cell_types <- c("B-cell",
                  "plasmablast")

my_cell_types <- c("macrophage",
                        "mast",
                        "mDC",
                        "monocyte",
                        "neutrophil",
                        "pDC")

str_cell_types <- subset(all_cell_types,
                           !(all_cell_types %in% imm_cell_types) &
                             (all_cell_types != "NotDet"))
                    

basic_cats <- function(x) {
  if(x %in% b_cell_types) { return('bcell') } else {
    if(x %in% cd4_tcell_types) { return('tcell_cd4') } else {
    if(x %in% cd8_tcell_types) { return('tcell_cd8') } else {
      if(x %in% my_cell_types) { return('mycell') } else {
        if(x %in% glomcell_types) {return('glomcell') } else {
          if(x %in% vesslcell_types) {return('vesslcell')} else {
            if(x %in% tubcell_types) {return('tubcell')} else {
              if(x %in% interstcell_types) {return('interstcell')} else {
                if(x %in% innate_lymph) {return('NKcell')}
                return("ERROR")
              }
            }
          }
        }
      }
    }
  }
  }
}

# organize metadata
annot <- merge(annot, data.frame(clust), by.x = "cell_ID", by.y = "row.names") 
# add cell calls
row.names(annot) <- annot$cell_ID
# annotate cells with larger cell type bins
annot$basictype <- sapply(annot$clust, basic_cats)
annot$alpha <- sapply(annot$basictype, function(x) {
  if(x %in% c('tcell', 'bcell', 'mycell')) {return(1)} else
    {return(0.2)}
})
# refine annotation of cd4 and cd8 t cells, to combine cells together
subset_tmp <- which(annot$basictype %in% c('tcell_cd4', 'tcell_cd8'))
annot[subset_tmp,'clust'] <- annot[subset_tmp,'basictype']


tmp <- as.data.frame(contam[,c(b_cell_types)])
tmp$maxval <- unlist(apply(tmp, 1, max))

ggplot(tmp, aes(x = maxval)) + geom_density()


# Define contaminated genes for B cells
b_cell_uncontam <- row.names(
  data.frame(!(contam[,b_cell_types])) %>% 
    filter_all(all_vars(.))
)

Compute PCA and generate UMAP

Will use Seurat to obtain UMAP to cluster cells

# Creat Seurat Object
## prepare all annotations
annot$context <- context[annot$cell_ID]
annot <- bind_cols(annot, cannot[annot$cell_ID,c('in.glom', 'inside.glom','position.vs.glom', 'closest.glom')])
## B-cells
bcell_seurat <- CreateSeuratObject(
  counts = raw[c(b_cell_uncontam, 'HBB'),],
  project = "LN_spatial",
  assay = "nanostrRNA",
  meta.data = annot
)

### only B-cell annotation
bcell_seurat <- subset(bcell_seurat,
                       subset = clust %in% b_cell_types)

# Scale data
bcell_seurat@meta.data$log10totalcounts <- sapply(bcell_seurat@meta.data$nCount_nanostrRNA, log10)
bcell_seurat <- ScaleData(bcell_seurat, 
                          features = c(b_cell_uncontam, 'HBB'),
                          model.use = 'negbinom',
                          vars.to.regress = 'log10totalcounts')
Regressing out log10totalcounts

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Centering and scaling data matrix

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## negative values in the Scale Data column correspond to 0 values in the expression data. Rather than let pseudocounts cause "negative gene expression", these values should be corrected to be zero
tru_val <- as.vector(bcell_seurat@assays$nanostrRNA@counts)
scaled <- as.vector(bcell_seurat@assays$nanostrRNA@scale.data)
toplot <- data.frame(counts = tru_val,
                     scaled = scaled)

ggplot(toplot, aes(x = counts, y = scaled)) + geom_point(alpha = 0.2, size = 0.2)


# Make all scaled values < 0 equal 0 
bcell_seurat@assays$nanostrRNA@scale.data[which(bcell_seurat@assays$nanostrRNA@scale.data < 0)] <- 0

# Filter HBB+ cells
## Dist
cells_in_data <- colnames(bcell_seurat)

tmp <- data.frame(cell_ID = cells_in_data,
                  HBB = bcell_seurat@assays$nanostrRNA@scale.data['HBB', cells_in_data],
                  HBA = bcell_seurat@assays$nanostrRNA@scale.data['HBA1', cells_in_data])

ggplot(tmp, aes(x = HBA, y = HBB)) + geom_point()


HB_cells <- tmp[which((tmp$HBA > 2.5) |
                        tmp$HBB > 2.5), 'cell_ID']
nonHB_cells <- tmp$cell_ID[which(!(tmp$cell_ID %in% HB_cells))]

### update annot to include rbcs
annot[which(annot$cell_ID %in% HB_cells),'basictype'] <- 'rbc'
annot[which(annot$cell_ID %in% HB_cells),'clust'] <- 'rbc'

### No HB cells
bcell_seurat <- subset(bcell_seurat,
                       subset = cell_ID %in% nonHB_cells)

### No hemoglobin gene expression
all_genes <- row.names(bcell_seurat)
bcell_seurat <- subset(bcell_seurat,
                       features = all_genes[which(!(all_genes %in% c('HBB', 'HBA1')))])
bcell_all.genes <- rownames(bcell_seurat)

# Run PCA
## B-cells
bcell_seurat <- RunPCA(bcell_seurat, features = bcell_all.genes, npcs=20)
PC_ 1 
Positive:  MARCO, MMP3, CCL7, CLEC4D, RSPO2, IL36G, FOXP3, MMP1, LY75, IFNG 
       PGF, CYP19A1, GPER1, ACKR1, IFNL3, NLRC4, IAPP, GDNF, EFNB3, ADGRV1 
       VPREB3, KRT6B, CD8B, S100A8, ADGRB3, TNFRSF11A, ADGRB2, INHBB, CD40LG, IL24 
Negative:  CD53, S100A4, IL16, PTGES2, SELENOP, IL17D, STAT5A, TNFRSF17, LAIR1, LIF 
       CD70, LGALS9, WIF1, WNT7B, RPL32, MPO, BTG1, CD52, EFNA4, HLA-DQB1 
       MTRNR2L1, KRT13, CCRL2, C1QB, TNFRSF9, CSK, RAC2, ARHGDIB, IL15RA, PSCA 
PC_ 2 
Positive:  KRT13, PSCA, LIF, EFNA4, IL17D, WNT7B, IL17A, TNFRSF9, CCRL2, PTGES2 
       TNFRSF17, STAT5A, CD70, MTRNR2L1, APOB, WIF1, MPO, LEP, TWIST2, KRT86 
       S100A4, LAIR1, CUZD1, KRT20, ADGRF4, RAD51, GDF3, CD53, IL20, LGALS9 
Negative:  XBP1, IFITM1, GPX1, MGP, COL3A1, IFI27, MZB1, C1QA, C1QC, CD81 
       TAGLN, CALD1, RPL34, HLA-DRB5, JCHAIN, IGKC, MALAT1, CD38, HSP90B1, COL1A1 
       BST2, CD163, CD27, IGHG2, TIMP1, HLA-DPA1, ITGB2, TYK2, IGHG1, SRGN 
PC_ 3 
Positive:  PROKR1, SERPINB5, ATF3, DNTT, VEGFC, TNFRSF13B, CXCR5, ACTG2, BMP6, CCL13 
       NLRP2, GDNF, NRIP3, CCL28, FGG, TCL1A, TNFSF13B, AATK, SLC2A4, MMP3 
       ADGRV1, COL9A3, TLR3, ACKR3, LINC02446, SAA2, WNT5B, EFNB3, THBS2, CCL7 
Negative:  KRT13, LIF, PTGES2, TNFRSF17, C1QB, CCRL2, STAT5A, TNFRSF9, S100A4, CD53 
       MTRNR2L1, MPO, EFNA4, WNT7B, IL17A, IL17D, SELENOP, LGALS9, CD70, LAIR1 
       WIF1, HLA-DQA1, C1QA, HLA-DPA1, C1QC, PSCA, CD163, ITGB2, HLA-DRB5, TIMP1 
PC_ 4 
Positive:  CCL5, GZMK, PTPRCAP, HLA-DQA1, FYB1, CD52, HLA-DPA1, HLA-DQB1, CD84, LYZ 
       CD2, CD37, NKG7, PRF1, PDCD1, ITGB2, NLRC5, CD3E, PTPRC, IL16 
       KLRK1, CD69, CST7, GZMH, ARHGDIB, IL2RG, BTG1, IL7R, GZMB, CASP8 
Negative:  MZB1, XBP1, TLR2, COL3A1, IGKC, CLEC4A, RPS4Y1, LPAR5, JCHAIN, MGP 
       PTGS2, IGHG2, SMARCB1, IGHG1, TNFAIP6, TAGLN, NRG4, NOD2, COL5A1, LUM 
       EPHB6, CSF1R, COL1A1, WNT5A, CD38, ANGPT2, BGN, HSP90B1, CALD1, TWIST1 
PC_ 5 
Positive:  FYN, CLEC4A, CSF1R, IL12RB1, RPS4Y1, NRG4, EPHB6, NOD2, CCL5, SMARCB1 
       CXCL17, GDF3, TLR2, IL20, CCL3, PLAC8, TWIST1, CTLA4, RAC2, ACKR3 
       COL15A1, FYB1, CD2, RGS1, IL7R, TNFAIP6, CLOCK, CXCR4, PTGIS, ANGPT2 
Negative:  TSLP, XBP1, MPO, MZB1, COL3A1, ADGRA3, IGHG1, PTGDR2, WNT7A, PDGFD 
       WNT9A, IGHG2, KRT13, COL1A1, COL1A2, WNT7B, FGF12, WIF1, DMBT1, VEGFC 
       TAGLN, TNFRSF17, MGP, TNFRSF9, IGKC, MMP1, COL5A2, UCP1, CD38, COL5A3 
ElbowPlot(bcell_seurat, ndims=20)

bcell_seurat <- RunUMAP(bcell_seurat, dims = 1:20)
Warning: The default method for RunUMAP has changed from calling Python UMAP via reticulate to the R-native UWOT using the cosine metric
To use Python UMAP via reticulate, set umap.method to 'umap-learn' and metric to 'correlation'
This message will be shown once per session
12:04:57 UMAP embedding parameters a = 0.9922 b = 1.112
12:04:57 Read 2897 rows and found 20 numeric columns
12:04:57 Using Annoy for neighbor search, n_neighbors = 30
12:04:57 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:04:58 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f3661fd7a4
12:04:58 Searching Annoy index using 1 thread, search_k = 3000
12:04:59 Annoy recall = 100%
12:04:59 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:05:00 Initializing from normalized Laplacian + noise (using RSpectra)
12:05:00 Commencing optimization for 500 epochs, with 124806 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:05:03 Optimization finished
# Run UMAP
## B-cells
bcell_seurat <- FindNeighbors(bcell_seurat, dims = 1:20)
Computing nearest neighbor graph
Computing SNN
bcell_seurat <- FindClusters(bcell_seurat, resolution = 1)
Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck

Number of nodes: 2897
Number of edges: 102784

Running Louvain algorithm...
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
Maximum modularity in 10 random starts: 0.6515
Number of communities: 10
Elapsed time: 0 seconds
bcell_seurat <- AddMetaData(bcell_seurat,
                  data.frame(bcell_seurat@reductions$umap@cell.embeddings))

DimPlot(bcell_seurat, reduction = 'umap') + plot_annotation(title='B-cell PCA Clusters')

ggplot(bcell_seurat@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=log10totalcounts)) +
  geom_point(size=0.5) +
  ggtitle('B-cell UMAP with RNA Counts')

NA
NA

Subcluster cells with MLE

Use MLEcell

# b cell subclustering
bcell_cols <- which(clust %in% b_cell_types)
bcell_cnts <- raw[b_cell_uncontam,bcell_cols]
bcell_negm <- annot[bcell_cols,'negmean']
bcell_coho <- fastCohorting(annot[bcell_cols, c('Area',
                                                'AspectRatio',
                                                'Mean.PanCK', 
                                                'Mean.CD45',
                                                'Mean.DAPI')],
                        gaussian_transform = TRUE) 
fitting ...

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bcell_unsup <- insitutype(counts = t(as.matrix(bcell_cnts)),
                          neg = bcell_negm,
                          cohort = bcell_coho,
                          bg = NULL, 
                    n_clusts = c(2, 4),
                    reference_profiles = NULL, # NULL value runs unsupervised clustering
                    ) 
1.1 cells per geometric bin.
Selecting optimal number of clusters from a range of 2 - 4
Clustering with n_clust = 2
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
Converged: <= 0.5% of cell type assignments changed in the last iteration.
==========================================================================
Clustering with n_clust = 4
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
Converged: <= 0.5% of cell type assignments changed in the last iteration.
==========================================================================
phase 1: random starts in 3000 cell subsets
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
iter 13
iter 14
iter 15
iter 16
iter 17
iter 18
iter 19
iter 20
iter 21
iter 22
iter 23
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
iter 13
iter 14
iter 15
iter 16
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
iter 13
iter 14
iter 15
iter 16
iter 17
iter 18
iter 19
iter 20
iter 21
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
iter 12
iter 13
iter 14
iter 15
iter 16
iter 17
iter 18
iter 19
iter 20
iter 21
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
iter 1
iter 2
iter 3
iter 4
iter 5
iter 6
iter 7
iter 8
iter 9
iter 10
iter 11
Converged: <= 0.2% of cell type assignments changed in the last iteration.
==========================================================================
phase 2: refining best random start in a 3000 cell subset
iter 1
iter 2
iter 3
iter 4
Converged: <= 0.1% of cell type assignments changed in the last iteration.
==========================================================================
phase 3: finalizing clusters in a 3000 cell subset
iter 1
iter 2
Converged: <= 0.01% of cell type assignments changed in the last iteration.
==========================================================================
phase 4: classifying all 3000 cells

MLE heatmap

# B-cell heatmap
str(bcell_unsup)
List of 5
 $ clust                      : Named chr [1:3000] "d" "a" "d" "d" ...
  ..- attr(*, "names")= chr [1:3000] "c_1_13_59" "c_1_13_878" "c_1_13_1019" "c_1_13_1046" ...
 $ prob                       : Named num [1:3000] 1 1 1 0.999 1 ...
  ..- attr(*, "names")= chr [1:3000] "c_1_13_59" "c_1_13_878" "c_1_13_1019" "c_1_13_1046" ...
 $ profiles                   : num [1:502, 1:4] 0.0565 0.0141 0.1469 0.0381 0.1174 ...
  ..- attr(*, "dimnames")=List of 2
  .. ..$ : chr [1:502] "AATK" "ACKR1" "ACKR3" "ACTG2" ...
  .. ..$ : chr [1:4] "a" "b" "c" "d"
 $ logliks                    : num [1:3000, 1:4] -260 -140 -237 -225 -226 ...
  ..- attr(*, "dimnames")=List of 2
  .. ..$ : chr [1:3000] "c_1_13_59" "c_1_13_878" "c_1_13_1019" "c_1_13_1046" ...
  .. ..$ : chr [1:4] "a" "b" "c" "d"
 $ logliks_from_lost_celltypes: num[1:3000, 0 ] 
  ..- attr(*, "dimnames")=List of 2
  .. ..$ : chr [1:3000] "c_1_13_59" "c_1_13_878" "c_1_13_1019" "c_1_13_1046" ...
  .. ..$ : NULL
round(head(bcell_unsup$prob),2)
  c_1_13_59  c_1_13_878 c_1_13_1019 c_1_13_1046 c_1_13_1195 c_1_13_1411 
          1           1           1           1           1           1 
bcell_hm <- heatmap(sweep(bcell_unsup$profiles,
                          1,
                          pmax(apply(bcell_unsup$profiles, 1, max),
                               .2),
                          "/"),
                    scale = "none",
                    main = "B-cell Subcluster Mean Expression Profiles")

Flightpath plot

## B-cells
# define cluster colors:
cols <- c('#a6cee3','#1f78b4','#b2df8a','#33a02c')
cols <- cols[seq_along(unique(bcell_unsup$clust))]
names(cols) <- unique(bcell_unsup$clust)

# make the flightpath plot
fp <- flightpath_plot(flightpath_result = NULL, insitutype_result = bcell_unsup, col = cols[bcell_unsup$clust])
Saving flightpath_plot to: ./NBClust-Plots/2024-10-24_12-07-11-PDT-flightpath_plot.png
class(fp)
[1] "gg"     "ggplot"
print(fp)
ggsave(fp, file="figures/bcell_MLEcell_fp.png")
Cannot find directory ]8;;file:///data/hps/home/nhasl2/LN_SpatialTranscriptomics/2024-April_NewData/figuresfigures]8;;.
ℹ Would you like to create a new directory?

1: Yes
2: No

Enter an item from the menu, or 0 to exit
1
✔ Created directory: ]8;;file:///data/hps/home/nhasl2/LN_SpatialTranscriptomics/2024-April_NewData/figuresfigures]8;;.
Saving 7.29 x 4.5 in image

Compare MLEcell and UMAP

# B-cells
bcell_seurat <- AddMetaData(bcell_seurat, 
                            data.frame(bcell_unsup$clust))

# rename subcluster identity
new = c('B.4','B.1','B.3','B.2')
new = factor(new, levels = c('B.1', 'B.2', 'B.3', 'B.4'))
key = data.frame(old = letters[1:4],
                 new = new)

bcell_seurat@meta.data$bcell_subclust <- sapply(bcell_seurat@meta.data$bcell_unsup.clust,
                                                function(o) {
                                                  return(key[which(key$old == o),'new'])
                                                })

bcell_seurat@meta.data$bcell_subclust <- factor(bcell_seurat@meta.data$bcell_subclust)

bcellcols <- c('#66c2a5','#fc8d62','#8da0cb','#e78ac3')

ggplot(bcell_seurat@meta.data,
       aes(x=UMAP_1,y=UMAP_2,color=bcell_subclust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols)

ggsave('figures/bcell_MLEcell_subclusts_UMAPspace.png',
       height=5.5)
Saving 7.29 x 5.5 in image

saveRDS(bcell_seurat, 
        file = 'processed_data/bcell_seurat.RDS')

Pub UMAP plot

Determine reasonable count filter

lapply(seq(from = 1.5, to = 2.5, by =0.1), function(x) {
  print(x)
  
  # filter and rescale the data
  temp_seurat <- ScaleData(subset(bcell_seurat, subset = log10totalcounts > x), 
                          features = c(bcell_all.genes),
                          model.use = 'negbinom',
                          vars.to.regress = 'log10totalcounts')
  # Run PCA
  temp_seurat <- RunPCA(temp_seurat, features = bcell_all.genes, npcs=20)
  # Run UMAP
  temp_seurat <- RunUMAP(temp_seurat, dims = 1:20)
  # Plot
  Idents(object = temp_seurat) <- temp_seurat@meta.data$'bcell_unsup.clust' 
  DimPlot(temp_seurat,
          reduction = 'umap',
          ) + plot_annotation(title=paste0('B-cell Subclusters, log RNA count >', x))
})
[1] 1.5
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGHG2, IGKC, IGHG1, XBP1, MALAT1, MZB1, MZT2A, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, JCHAIN, GPX1, CALD1, C1QA, CD38, CD81, IFI27, TAGLN 
       RPL34, C1QC, COL1A1, IGHA1, FKBP11, CD27, BST2, TIMP1, HLA-DRB5, IRF4 
Negative:  PSCA, IL17D, EFNA4, LIF, WNT7B, KRT13, STAT5A, TNFRSF9, CD70, PTGES2 
       TNFRSF17, IL17A, CCRL2, MTRNR2L1, APOB, WIF1, LEP, CD53, TWIST2, S100A4 
       CUZD1, RAD51, TCL1A, KRT20, KRT86, RARG, SLC2A4, WNT9A, LGALS9, CLEC4A 
PC_ 2 
Positive:  KRT13, LIF, PTGES2, CCRL2, MPO, TNFRSF17, TNFRSF9, IL17A, STAT5A, MTRNR2L1 
       EFNA4, IL17D, WNT7B, LAIR1, WIF1, CD70, IGHG1, S100A4, PSCA, SELENOP 
       C1QB, IGHG2, CD53, LGALS9, IGKC, APOB, KRT86, MKI67, ELANE, MZB1 
Negative:  PTPRCAP, CXCR5, CD37, HLA-DQB1, CD69, TNFSF13B, KRT15, IL2RG, CXCR4, PTPRC 
       IL2RB, TNFSF12, HLA-DRB5, CD48, MZT2A, TNFRSF13B, ARHGDIB, MRC1, CD44, RUNX3 
       CSK, LYZ, GPR183, ACTG2, VEGFC, JAK2, FES, LINC02446, OASL, GZMH 
PC_ 3 
Positive:  HLA-DPA1, HLA-DQA1, C1QB, HLA-DRB5, C1QA, HLA-DQB1, C1QC, ITGB2, CCL5, CD53 
       LYZ, S100A4, FYB1, CD163, CD68, CD52, KRT13, CD37, IL16, STAT5A 
       CD2, LGALS9, PTPRCAP, NLRC5, LIF, PTGES2, CD3E, MALAT1, PTPRC, GPX1 
Negative:  MZB1, XBP1, IGHG2, IGHG1, LPAR5, IGKC, TNFAIP6, RPS4Y1, TLR2, WNT5A 
       JCHAIN, SMARCB1, COL3A1, CD38, PLA2R1, CLEC4A, PTGS2, ADGRV1, COL5A1, DNTT 
       MGP, TAGLN, CSF2, COL1A1, ATF3, IRF4, AGR2, TSLP, FKBP11, HSP90B1 
PC_ 4 
Positive:  WNT7A, PTGDR2, VEGFC, TSLP, IGHG1, ADGRA3, WNT9A, IGHG2, CXCR5, WIF1 
       IL12A, KRT13, WNT7B, FGF12, DMBT1, FGG, TNFRSF9, SERPINB5, GZMH, FZD6 
       MMP1, TNFRSF13B, CD5L, ADGRG5, NRIP3, ATF3, MPO, TNFRSF17, IL17D, XCL2 
Negative:  CSF1R, CLEC4A, TLR2, RPS4Y1, FYN, NOD2, IL12RB1, NRG4, SMARCB1, EPHB6 
       CXCL17, TWIST1, CCL3, IL20, GDF3, COL15A1, PTGS2, RAC2, PLAC8, TNFAIP6 
       CLOCK, CTLA4, ANGPT2, IL15RA, ACKR3, PTGIS, WNT5A, NANOG, AZU1, RGS1 
PC_ 5 
Positive:  TAGLN, COL3A1, MGP, COL1A1, LUM, COL1A2, DCN, C1QC, COL6A2, C1QA 
       TIMP1, CD81, MMP2, C1QB, CALD1, SELENOP, CD163, CXCL12, BGN, COL6A3 
       PDGFRA, CD68, HGF, SLC40A1, SNAI2, MS4A4A, CYP1B1, IGFBP6, GPX1, MRC2 
Negative:  MZB1, MZT2A, MALAT1, CD27, XBP1, CD38, FKBP11, CCL5, IL2RG, DUSP5 
       FYN, CD3E, IRF4, JCHAIN, ST6GAL1, IGHG2, KLF2, HSP90B1, CD8A, NLRC5 
       CST7, CD52, IGHA1, CD79A, ITGAL, DUSP2, RAC2, GAS6, CSF2RB, GZMA 
12:08:03 UMAP embedding parameters a = 0.9922 b = 1.112
12:08:03 Read 2724 rows and found 20 numeric columns
12:08:03 Using Annoy for neighbor search, n_neighbors = 30
12:08:03 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:08:03 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f33b060159
12:08:03 Searching Annoy index using 1 thread, search_k = 3000
12:08:04 Annoy recall = 100%
12:08:04 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:08:05 Initializing from normalized Laplacian + noise (using RSpectra)
12:08:05 Commencing optimization for 500 epochs, with 111790 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:08:08 Optimization finished
[1] 1.6
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGHG2, IGKC, IGHG1, MALAT1, XBP1, MZB1, MZT2A, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, JCHAIN, GPX1, CALD1, CD38, C1QA, CD81, IFI27, TAGLN 
       RPL34, C1QC, COL1A1, IGHA1, FKBP11, CD27, BST2, TIMP1, HLA-DRB5, IRF4 
Negative:  PSCA, IL17D, EFNA4, LIF, WNT7B, KRT13, STAT5A, CD70, TNFRSF9, PTGES2 
       TNFRSF17, IL17A, CCRL2, MTRNR2L1, APOB, CD53, LEP, WIF1, TWIST2, S100A4 
       CUZD1, RAD51, KRT20, KRT86, TCL1A, SLC2A4, RARG, LGALS9, CLEC4A, WNT9A 
PC_ 2 
Positive:  LIF, KRT13, MPO, PTGES2, CCRL2, TNFRSF17, TNFRSF9, IL17A, MTRNR2L1, STAT5A 
       EFNA4, IL17D, LAIR1, WNT7B, IGHG1, WIF1, CD70, PSCA, S100A4, IGHG2 
       SELENOP, C1QB, CD53, IGKC, LGALS9, APOB, KRT86, MZB1, ELANE, MKI67 
Negative:  PTPRCAP, CXCR5, HLA-DQB1, CD37, CD69, KRT15, PTPRC, IL2RG, HLA-DRB5, CXCR4 
       IL2RB, TNFSF13B, TNFSF12, MZT2A, CD48, CD44, ARHGDIB, LYZ, TNFRSF13B, BTG1 
       MRC1, GPR183, RUNX3, FES, CSK, VEGFC, NLRC5, ACTG2, OASL, SELL 
PC_ 3 
Positive:  MZB1, XBP1, IGHG2, LPAR5, IGHG1, IGKC, TNFAIP6, RPS4Y1, TLR2, WNT5A 
       JCHAIN, SMARCB1, PLA2R1, CD38, COL3A1, PTGS2, CLEC4A, ADGRV1, DNTT, ATF3 
       AGR2, TAGLN, COL5A1, CSF2, MGP, IRF4, PROKR1, FKBP11, CLOCK, HSP90B1 
Negative:  HLA-DPA1, HLA-DQA1, C1QB, HLA-DRB5, C1QA, HLA-DQB1, C1QC, ITGB2, CCL5, CD53 
       LYZ, S100A4, CD163, FYB1, CD68, KRT13, CD52, STAT5A, LIF, IL16 
       CD37, LGALS9, PTGES2, CD2, NLRC5, PTPRCAP, CD3E, MALAT1, CCRL2, EFNA4 
PC_ 4 
Positive:  WNT7A, PTGDR2, VEGFC, IGHG1, TSLP, ADGRA3, WNT9A, IGHG2, CXCR5, KRT13 
       WIF1, WNT7B, IL12A, FGF12, GZMH, FZD6, MMP1, FGG, CD5L, TNFRSF9 
       TNFRSF13B, DMBT1, SERPINB5, NRIP3, ADGRG5, ATF3, TNFRSF17, WNT5B, MPO, XCL2 
Negative:  CSF1R, CLEC4A, TLR2, RPS4Y1, FYN, NOD2, IL12RB1, NRG4, SMARCB1, EPHB6 
       CXCL17, TWIST1, CCL3, IL20, GDF3, COL15A1, PTGS2, PLAC8, RAC2, TNFAIP6 
       CLOCK, CTLA4, ANGPT2, IL15RA, PTGIS, ACKR3, NANOG, WNT5A, AZU1, RGS1 
PC_ 5 
Positive:  TAGLN, COL3A1, COL1A1, MGP, LUM, COL1A2, DCN, C1QC, COL6A2, C1QA 
       TIMP1, CD81, MMP2, CALD1, C1QB, CXCL12, SELENOP, CD163, BGN, COL6A3 
       PDGFRA, CD68, HGF, SLC40A1, SNAI2, MS4A4A, IGFBP6, CYP1B1, MRC2, GPX1 
Negative:  MZB1, MZT2A, MALAT1, CD27, XBP1, CD38, CCL5, FKBP11, IL2RG, FYN 
       DUSP5, CD3E, IRF4, JCHAIN, ST6GAL1, IGHG2, CD8A, KLF2, NLRC5, RAC2 
       HSP90B1, CST7, CD79A, DUSP2, CSF2RB, ITGAL, IGHA1, GAS6, CD52, CCR5 
12:08:42 UMAP embedding parameters a = 0.9922 b = 1.112
12:08:42 Read 2606 rows and found 20 numeric columns
12:08:42 Using Annoy for neighbor search, n_neighbors = 30
12:08:42 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:08:42 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f36f4fec5
12:08:42 Searching Annoy index using 1 thread, search_k = 3000
12:08:42 Annoy recall = 100%
12:08:43 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:08:44 Initializing from normalized Laplacian + noise (using RSpectra)
12:08:44 Commencing optimization for 500 epochs, with 106558 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:08:47 Optimization finished
[1] 1.7
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGHG2, IGKC, IGHG1, MALAT1, XBP1, MZB1, MZT2A, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, JCHAIN, GPX1, CALD1, CD38, C1QA, CD81, TAGLN, IFI27 
       RPL34, C1QC, IGHA1, COL1A1, FKBP11, CD27, BST2, TIMP1, HLA-DRB5, IRF4 
Negative:  PSCA, IL17D, EFNA4, LIF, WNT7B, KRT13, STAT5A, CD70, TNFRSF9, PTGES2 
       IL17A, TNFRSF17, CCRL2, MTRNR2L1, APOB, CD53, WIF1, LEP, TWIST2, S100A4 
       CUZD1, KRT20, RAD51, TCL1A, RARG, KRT86, SLC2A4, LGALS9, GDF3, CTSW 
PC_ 2 
Positive:  PTPRCAP, HLA-DQB1, CD37, CXCR5, CD69, CXCR4, HLA-DRB5, PTPRC, KRT15, IL2RG 
       IL2RB, TNFSF12, TNFSF13B, CD48, ARHGDIB, MZT2A, LYZ, CD44, MRC1, HLA-DPA1 
       ITGB2, FES, BTG1, GPR183, NLRC5, RUNX3, TNFRSF13B, JAK2, CSK, SELL 
Negative:  LIF, KRT13, MPO, PTGES2, CCRL2, TNFRSF17, IL17A, TNFRSF9, MTRNR2L1, EFNA4 
       STAT5A, IL17D, LAIR1, WNT7B, IGHG1, WIF1, CD70, PSCA, IGHG2, S100A4 
       SELENOP, C1QB, IGKC, CD53, LGALS9, APOB, KRT86, MZB1, LPAR5, ELANE 
PC_ 3 
Positive:  HLA-DPA1, HLA-DQA1, C1QB, C1QA, HLA-DRB5, C1QC, HLA-DQB1, ITGB2, CCL5, CD53 
       S100A4, LYZ, CD163, FYB1, KRT13, CD68, STAT5A, LIF, PTGES2, CD52 
       LGALS9, IL16, CD37, CD2, CCRL2, NLRC5, EFNA4, TNFRSF9, TNFRSF17, PTPRCAP 
Negative:  MZB1, XBP1, IGHG2, LPAR5, RPS4Y1, TNFAIP6, IGKC, IGHG1, TLR2, WNT5A 
       JCHAIN, PLA2R1, SMARCB1, CD38, COL3A1, CLEC4A, ADGRV1, DNTT, PTGS2, ATF3 
       TAGLN, AGR2, MGP, CSF2, PROKR1, COL1A1, COL5A1, TWIST1, CLOCK, ACKR3 
PC_ 4 
Positive:  WNT7A, VEGFC, PTGDR2, IGHG1, TSLP, IGHG2, WNT9A, KRT13, CXCR5, WIF1 
       WNT7B, ADGRA3, GZMH, FGG, FGF12, IL12A, CD5L, FZD6, DMBT1, TNFRSF9 
       NRIP3, MMP1, TNFRSF13B, WNT5B, IL17D, TNFRSF17, TNFSF9, ATF3, SERPINB5, EFNA4 
Negative:  CSF1R, CLEC4A, TLR2, RPS4Y1, NOD2, FYN, IL12RB1, NRG4, SMARCB1, EPHB6 
       CXCL17, CCL3, TWIST1, IL20, GDF3, COL15A1, TNFAIP6, PTGS2, PLAC8, RAC2 
       CLOCK, CTLA4, ANGPT2, IL15RA, ACKR3, PTGIS, NANOG, AZU1, WNT5A, C1QC 
PC_ 5 
Positive:  TAGLN, COL1A1, COL3A1, MGP, LUM, COL1A2, DCN, COL6A2, C1QC, TIMP1 
       C1QA, CD81, MMP2, CALD1, CXCL12, BGN, SELENOP, COL6A3, C1QB, CD163 
       PDGFRA, HGF, CD68, SLC40A1, SNAI2, IGFBP6, CYP1B1, MS4A4A, MRC2, NGFR 
Negative:  MZB1, CD27, MALAT1, MZT2A, XBP1, CD38, CCL5, IL2RG, FKBP11, FYN 
       DUSP5, JCHAIN, ST6GAL1, IGHG2, CD3E, IRF4, CST7, CD8A, HSP90B1, RAC2 
       KLF2, GAS6, ITGAL, NLRC5, IGHA1, GZMA, DUSP2, CCR2, CD79A, CSF2RB 
12:09:18 UMAP embedding parameters a = 0.9922 b = 1.112
12:09:18 Read 2470 rows and found 20 numeric columns
12:09:18 Using Annoy for neighbor search, n_neighbors = 30
12:09:18 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:09:18 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f33784dace
12:09:18 Searching Annoy index using 1 thread, search_k = 3000
12:09:19 Annoy recall = 100%
12:09:20 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:09:21 Initializing from normalized Laplacian + noise (using RSpectra)
12:09:21 Commencing optimization for 500 epochs, with 101004 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:09:23 Optimization finished
[1] 1.8
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, XBP1, MALAT1, MZB1, MZT2A, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, JCHAIN, GPX1, CD38, CALD1, TAGLN, C1QA, CD81, IFI27 
       RPL34, C1QC, FKBP11, IGHA1, COL1A1, CD27, BST2, TIMP1, IRF4, HLA-DRB5 
Negative:  PSCA, IL17D, LIF, EFNA4, WNT7B, KRT13, STAT5A, TNFRSF9, IL17A, CD70 
       TNFRSF17, PTGES2, CCRL2, MTRNR2L1, CD53, APOB, WIF1, TWIST2, LEP, S100A4 
       KRT20, RAD51, CUZD1, TCL1A, RARG, LGALS9, SLC2A4, GDF3, CTSW, KRT86 
PC_ 2 
Positive:  PTPRCAP, HLA-DQB1, HLA-DRB5, CD37, CD69, CXCR5, CXCR4, IL2RG, PTPRC, LYZ 
       KRT15, HLA-DPA1, TNFSF12, ARHGDIB, CD44, ITGB2, CD48, MZT2A, IL2RB, TNFSF13B 
       NLRC5, BTG1, CD52, MRC1, FES, JAK2, GPR183, RUNX3, CD3E, CCL5 
Negative:  LIF, KRT13, MPO, PTGES2, CCRL2, TNFRSF17, IL17A, TNFRSF9, MTRNR2L1, EFNA4 
       IL17D, IGHG1, STAT5A, LAIR1, WIF1, WNT7B, IGHG2, CD70, PSCA, S100A4 
       SELENOP, IGKC, C1QB, APOB, LGALS9, CD53, MZB1, LPAR5, KRT86, XBP1 
PC_ 3 
Positive:  HLA-DPA1, HLA-DQA1, C1QB, C1QA, C1QC, HLA-DRB5, HLA-DQB1, ITGB2, CD53, CCL5 
       S100A4, LYZ, KRT13, CD163, LIF, STAT5A, FYB1, PTGES2, CD68, LGALS9 
       CCRL2, CD52, EFNA4, CD2, TNFRSF9, IL16, TNFRSF17, CD37, MTRNR2L1, NLRC5 
Negative:  MZB1, XBP1, LPAR5, RPS4Y1, IGHG2, TNFAIP6, IGKC, WNT5A, TLR2, PLA2R1 
       CD38, SMARCB1, JCHAIN, IGHG1, DNTT, ADGRV1, ATF3, AGR2, PTGS2, COL3A1 
       PROKR1, TSLP, COL1A1, TAGLN, CLEC4A, ACKR3, IRF4, CSF2, MGP, THBS2 
PC_ 4 
Positive:  WNT7A, PTGDR2, IGHG1, VEGFC, WIF1, TSLP, KRT13, IGHG2, ADGRA3, GZMH 
       WNT7B, CXCR5, CD5L, TNFRSF9, FGG, WNT9A, TNFRSF17, FZD6, FGF12, IL17D 
       IL12A, NRIP3, DMBT1, MMP1, TNFSF9, ADGRG5, WNT5B, EFNA4, STAT5A, RB1 
Negative:  CSF1R, CLEC4A, TLR2, RPS4Y1, SMARCB1, IL12RB1, FYN, NOD2, NRG4, CXCL17 
       EPHB6, TWIST1, CCL3, GDF3, IL20, TNFAIP6, CTLA4, PTGS2, PLAC8, COL15A1 
       RAC2, IL15RA, CLOCK, PTGIS, AZU1, ACKR3, ANGPT2, NANOG, WNT5A, C1QC 
PC_ 5 
Positive:  MZB1, CD27, MZT2A, XBP1, MALAT1, CD38, CCL5, FYN, IL2RG, FKBP11 
       IGHG2, DUSP5, CD3E, ST6GAL1, CD8A, CST7, IRF4, GAS6, RAC2, ITGAL 
       GZMA, NLRC5, CCR2, CCR5, JCHAIN, KLF2, HMGN2, NKG7, CD52, DUSP2 
Negative:  TAGLN, COL3A1, COL1A1, MGP, LUM, COL1A2, DCN, COL6A2, C1QC, TIMP1 
       CD81, C1QA, CALD1, MMP2, CXCL12, COL6A3, SELENOP, BGN, C1QB, CD163 
       PDGFRA, HGF, CD68, SLC40A1, SNAI2, IGFBP6, CYP1B1, MRC2, MS4A4A, NGFR 
12:09:52 UMAP embedding parameters a = 0.9922 b = 1.112
12:09:52 Read 2263 rows and found 20 numeric columns
12:09:52 Using Annoy for neighbor search, n_neighbors = 30
12:09:52 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:09:52 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f367cad289
12:09:52 Searching Annoy index using 1 thread, search_k = 3000
12:09:53 Annoy recall = 100%
12:09:53 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:09:54 Initializing from normalized Laplacian + noise (using RSpectra)
12:09:54 Commencing optimization for 500 epochs, with 92020 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:09:57 Optimization finished
[1] 1.9
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, MALAT1, XBP1, MZT2A, MZB1, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, JCHAIN, GPX1, CALD1, CD38, TAGLN, C1QA, CD81, IFI27 
       RPL34, C1QC, FKBP11, COL1A1, IGHA1, CD27, BST2, TIMP1, IRF4, HLA-DRB5 
Negative:  PSCA, IL17D, EFNA4, LIF, WNT7B, STAT5A, KRT13, IL17A, CD70, TNFRSF9 
       TNFRSF17, PTGES2, CCRL2, MTRNR2L1, CD53, APOB, WIF1, TWIST2, LEP, CUZD1 
       S100A4, TCL1A, RAD51, KRT20, SLC2A4, RARG, LGALS9, KRT86, CTSW, GDF3 
PC_ 2 
Positive:  PTPRCAP, HLA-DRB5, HLA-DQB1, CD69, CXCR5, CXCR4, IL2RG, CD37, KRT15, PTPRC 
       LYZ, ITGB2, CD44, CD48, HLA-DPA1, ARHGDIB, IL2RB, TNFSF12, NLRC5, MRC1 
       TNFSF13B, JAK2, CD52, BTG1, MZT2A, GPR183, FES, IL10RA, RUNX3, CD3E 
Negative:  LIF, MPO, KRT13, PTGES2, CCRL2, TNFRSF17, IL17A, TNFRSF9, MTRNR2L1, EFNA4 
       IL17D, IGHG1, STAT5A, LAIR1, WNT7B, WIF1, IGHG2, CD70, PSCA, S100A4 
       SELENOP, IGKC, C1QB, CD53, LGALS9, APOB, MZB1, LPAR5, KRT86, XBP1 
PC_ 3 
Positive:  MZB1, XBP1, LPAR5, IGHG2, RPS4Y1, TNFAIP6, TLR2, WNT5A, PLA2R1, CD38 
       IGKC, ATF3, IGHG1, COL3A1, SMARCB1, DNTT, JCHAIN, ADGRV1, AGR2, PROKR1 
       TAGLN, TSLP, IRF4, COL1A1, PTGS2, FKBP11, CSF2, BMP6, THBS2, GC 
Negative:  HLA-DPA1, HLA-DQA1, C1QB, C1QC, C1QA, HLA-DRB5, HLA-DQB1, ITGB2, CD53, S100A4 
       CCL5, LYZ, CD163, KRT13, LIF, STAT5A, PTGES2, FYB1, CD68, LGALS9 
       CCRL2, EFNA4, TNFRSF9, CD2, CD52, IL16, MTRNR2L1, CD37, TNFRSF17, NLRC5 
PC_ 4 
Positive:  WNT7A, PTGDR2, KRT13, TSLP, VEGFC, WIF1, IGHG1, IGHG2, GZMH, TNFRSF17 
       FZD6, CD5L, CXCR5, WNT7B, TNFRSF9, ADGRA3, MMP1, IL12A, WNT9A, FGF12 
       FGG, IL17D, ADGRG5, XCL2, LIF, WNT5B, NRIP3, DMBT1, STAT5A, TNFSF9 
Negative:  CSF1R, CLEC4A, RPS4Y1, TLR2, SMARCB1, IL12RB1, NRG4, CXCL17, FYN, EPHB6 
       NOD2, TWIST1, GDF3, CCL3, IL20, TNFAIP6, PTGIS, CTLA4, IL15RA, RAC2 
       PTGS2, CLOCK, COL15A1, AZU1, PLAC8, ACKR3, NANOG, ANGPT2, LUM, WNT5A 
PC_ 5 
Positive:  TAGLN, COL1A1, COL3A1, MGP, LUM, COL1A2, DCN, COL6A2, CD81, CALD1 
       TIMP1, C1QC, CXCL12, COL6A3, BGN, SELENOP, MMP2, C1QA, PDGFRA, C1QB 
       CD163, HGF, CD68, SLC40A1, SNAI2, IGFBP6, CYP1B1, MRC2, MS4A4A, PTGDS 
Negative:  MZB1, CD27, XBP1, CD38, MZT2A, MALAT1, CCL5, IL2RG, FKBP11, FYN 
       DUSP5, CST7, IGHG2, GZMA, CD3E, ST6GAL1, CD8A, JCHAIN, RAC2, IRF4 
       GAS6, NLRC5, CCR2, ITGAL, CCR5, ICOS, IGHA1, CD79A, NKG7, CD52 
12:10:23 UMAP embedding parameters a = 0.9922 b = 1.112
12:10:23 Read 2040 rows and found 20 numeric columns
12:10:23 Using Annoy for neighbor search, n_neighbors = 30
12:10:23 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:10:23 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f329243be0
12:10:23 Searching Annoy index using 1 thread, search_k = 3000
12:10:23 Annoy recall = 100%
12:10:24 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:10:25 Initializing from normalized Laplacian + noise (using RSpectra)
12:10:25 Commencing optimization for 500 epochs, with 82602 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:10:27 Optimization finished
[1] 2
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, MALAT1, MZT2A, XBP1, MZB1, TYK2, IFITM1, MGP 
       COL3A1, HSP90B1, CD38, GPX1, JCHAIN, CALD1, CD81, TAGLN, C1QA, IFI27 
       RPL34, FKBP11, COL1A1, C1QC, IGHA1, CD27, BST2, TIMP1, LPAR5, IRF4 
Negative:  PSCA, IL17D, EFNA4, WNT7B, LIF, STAT5A, KRT13, IL17A, CD70, TNFRSF9 
       TNFRSF17, PTGES2, CCRL2, MTRNR2L1, CD53, TWIST2, APOB, WIF1, SLC2A4, LEP 
       CUZD1, TCL1A, KRT20, RAD51, RARG, S100A4, LGALS9, CLEC4E, CTSW, KRT86 
PC_ 2 
Positive:  MPO, LIF, PTGES2, KRT13, IL17A, CCRL2, TNFRSF17, IGHG1, TNFRSF9, IGHG2 
       IL17D, LAIR1, MTRNR2L1, EFNA4, WIF1, STAT5A, WNT7B, PSCA, IGKC, CD70 
       SELENOP, MZB1, S100A4, APOB, LPAR5, XBP1, KRT86, EPHB6, IL20, TLR2 
Negative:  HLA-DRB5, HLA-DQB1, PTPRCAP, LYZ, ITGB2, HLA-DPA1, CD37, KRT15, PTPRC, CXCR4 
       CD52, CD69, CXCR5, HLA-DQA1, NLRC5, IL2RG, CD44, FYB1, CD48, ARHGDIB 
       IL10RA, BTG1, CD68, IL16, ZFP36, MRC1, CD163, CCL5, MZT2A, CD3E 
PC_ 3 
Positive:  MZB1, XBP1, PLA2R1, LPAR5, ATF3, AGR2, CD38, RPS4Y1, DNTT, TNFAIP6 
       ADGRV1, PROKR1, WNT5A, TLR2, COL3A1, VEGFC, TNFRSF13B, JCHAIN, TSLP, COL1A1 
       GAS6, IRF4, THBS2, CCL13, NRIP3, CAV1, FGF12, SERPINB5, TAGLN, SMARCB1 
Negative:  HLA-DPA1, C1QB, HLA-DQA1, C1QC, C1QA, CD53, S100A4, HLA-DRB5, HLA-DQB1, ITGB2 
       LIF, KRT13, PTGES2, STAT5A, CCL5, CCRL2, CD163, TNFRSF9, LYZ, EFNA4 
       MTRNR2L1, FYB1, CD68, LGALS9, TNFRSF17, IL17D, SELENOP, WNT7B, CD2, IL16 
PC_ 4 
Positive:  KRT13, WNT7A, WIF1, TSLP, IGHG2, IGHG1, PTGDR2, TNFRSF9, TNFRSF17, GZMH 
       VEGFC, IL12A, FZD6, FGG, MMP1, IL17D, WNT7B, CXCR5, WNT9A, CD5L 
       LIF, ADGRG5, ADGRA3, MPO, MZB1, XCL2, STAT5A, TNFRSF13B, KRT16, TNFSF9 
Negative:  CSF1R, CLEC4A, RPS4Y1, TLR2, SMARCB1, NRG4, CXCL17, EPHB6, IL12RB1, FYN 
       NOD2, IL20, TWIST1, GDF3, CCL3, TNFAIP6, LUM, PTGIS, RAC2, COL15A1 
       CTLA4, IL15RA, PTGS2, ACKR3, AZU1, CLOCK, WNT5A, CD163, NANOG, ANGPT2 
PC_ 5 
Positive:  MZB1, CD27, XBP1, FYN, CD38, MALAT1, CCL5, MZT2A, FKBP11, IL2RG 
       RAC2, GZMA, CST7, PLAC8, JCHAIN, DUSP5, CCR2, IRF4, CD8A, GAS6 
       ST6GAL1, IL6R, RPS4Y1, HSP90B1, NLRC5, ICOS, IGHA1, CD3E, CCR5, IGHG2 
Negative:  COL1A1, TAGLN, COL3A1, COL1A2, MGP, DCN, LUM, COL6A2, CXCL12, CALD1 
       COL6A3, SELENOP, CD81, BGN, TIMP1, MMP2, C1QA, C1QC, PDGFRA, HGF 
       C1QB, SNAI2, CD163, IGFBP6, SLC40A1, CYP1B1, CD68, MRC2, PTGDS, COL5A2 
12:10:50 UMAP embedding parameters a = 0.9922 b = 1.112
12:10:50 Read 1731 rows and found 20 numeric columns
12:10:50 Using Annoy for neighbor search, n_neighbors = 30
12:10:50 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:10:50 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f357ac0238
12:10:50 Searching Annoy index using 1 thread, search_k = 3000
12:10:50 Annoy recall = 100%
12:10:51 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:10:52 Initializing from normalized Laplacian + noise (using RSpectra)
12:10:52 Commencing optimization for 500 epochs, with 69420 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:10:54 Optimization finished
[1] 2.1
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, MZT2A, MALAT1, XBP1, MZB1, TYK2, MGP, IFITM1 
       COL3A1, HSP90B1, GPX1, CD38, CALD1, JCHAIN, C1QA, CD81, TAGLN, IFI27 
       RPL34, C1QC, FKBP11, COL1A1, IGHA1, CD27, BST2, TIMP1, LPAR5, IRF4 
Negative:  PSCA, IL17D, EFNA4, WNT7B, STAT5A, LIF, KRT13, IL17A, TNFRSF17, CD70 
       TNFRSF9, PTGES2, TWIST2, MTRNR2L1, SLC2A4, CCRL2, RAD51, TCL1A, LEP, CUZD1 
       CD53, APOB, RARG, KRT20, WIF1, CLEC4E, CTSW, LGALS9, KRT86, WNT9A 
PC_ 2 
Positive:  HLA-DQB1, HLA-DRB5, ITGB2, LYZ, PTPRCAP, HLA-DPA1, PTPRC, HLA-DQA1, CD52, CD37 
       CXCR5, CD163, NLRC5, FYB1, KRT15, CD68, CD69, ARHGDIB, CXCR4, IL2RG 
       BTG1, IL10RA, CCL5, ZFP36, CD48, CD3E, C1QA, TGFB1, IL16, GPR183 
Negative:  MPO, IL17A, LIF, PTGES2, IGHG1, CCRL2, KRT13, TNFRSF17, IGHG2, MTRNR2L1 
       LAIR1, IL17D, TNFRSF9, EFNA4, IGKC, PSCA, WIF1, STAT5A, MZB1, WNT7B 
       CD70, LPAR5, XBP1, APOB, RPS4Y1, KRT86, EPHB6, SELENOP, IL20, TLR2 
PC_ 3 
Positive:  MZB1, XBP1, PLA2R1, ATF3, AGR2, TNFRSF13B, DNTT, CD38, LPAR5, ADGRV1 
       COL1A1, VEGFC, COL3A1, PROKR1, CAV1, GAS6, NRIP3, ADORA2A, FGF12, IRF4 
       CCL13, TNFAIP6, RPS4Y1, CD27, PTGDR2, ST6GAL1, GC, WNT5A, TSLP, MGP 
Negative:  C1QB, HLA-DPA1, HLA-DQA1, C1QC, C1QA, LIF, PTGES2, S100A4, CD53, KRT13 
       HLA-DRB5, HLA-DQB1, ITGB2, STAT5A, CCRL2, EFNA4, MTRNR2L1, CD163, TNFRSF9, CCL5 
       TNFRSF17, LYZ, IL17D, FYB1, LGALS9, CD68, SELENOP, WNT7B, IL17A, CD2 
PC_ 4 
Positive:  CSF1R, CLEC4A, RPS4Y1, CXCL17, SMARCB1, TLR2, NRG4, EPHB6, IL12RB1, FYN 
       NOD2, IL20, TWIST1, LUM, PTGIS, CCL3, GDF3, TNFAIP6, COL15A1, CTLA4 
       RAC2, CLOCK, TIMP1, PTGS2, IL15RA, CD81, AZU1, CD163, NANOG, PLAC8 
Negative:  KRT13, IGHG1, IGHG2, WNT7A, WIF1, TNFRSF17, TSLP, TNFRSF9, PTGDR2, LIF 
       WNT7B, MPO, FZD6, GZMH, MZB1, MMP1, VEGFC, ADGRA3, IL12A, FGG 
       CD5L, IL17D, XBP1, CCRL2, IL17A, CXCR5, GAS6, WNT9A, ADGRG5, TNFRSF13B 
PC_ 5 
Positive:  COL1A1, COL3A1, COL1A2, TAGLN, MGP, LUM, COL6A2, DCN, CALD1, SELENOP 
       COL6A3, CXCL12, BGN, CD81, MMP2, TIMP1, PDGFRA, HGF, C1QB, C1QC 
       C1QA, SLC40A1, SNAI2, CYP1B1, IGFBP6, PTGDS, MRC2, CFD, COL14A1, CD163 
Negative:  CD27, MZB1, FYN, XBP1, CD38, CCL5, RAC2, IL2RG, GZMA, PLAC8 
       RGS1, CST7, RPS4Y1, FKBP11, CXCL17, MALAT1, NLRC5, MZT2A, GAS6, NOD2 
       ST6GAL1, CLOCK, DUSP5, ITGAL, CLEC4A, IGHG2, SEC61G, CCR2, FFAR4, PRSS2 
12:11:12 UMAP embedding parameters a = 0.9922 b = 1.112
12:11:12 Read 1407 rows and found 20 numeric columns
12:11:12 Using Annoy for neighbor search, n_neighbors = 30
12:11:12 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:12 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f31b1326f
12:11:12 Searching Annoy index using 1 thread, search_k = 3000
12:11:13 Annoy recall = 100%
12:11:13 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:11:14 Initializing from normalized Laplacian + noise (using RSpectra)
12:11:14 Commencing optimization for 500 epochs, with 55806 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:16 Optimization finished
[1] 2.2
Regressing out log10totalcounts

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGHG2, IGKC, IGHG1, MZT2A, MALAT1, XBP1, MZB1, TYK2, IFITM1, MGP 
       COL3A1, HSP90B1, GPX1, CALD1, CD38, C1QA, IFI27, JCHAIN, CD81, RPL34 
       C1QC, TAGLN, FKBP11, COL1A1, IGHA1, BST2, CD27, HLA-DRB5, TIMP1, LPAR5 
Negative:  PSCA, IL17D, EFNA4, STAT5A, WNT7B, LIF, TNFRSF17, IL17A, CD70, KRT13 
       TNFRSF9, TWIST2, SLC2A4, PTGES2, TCL1A, RARG, RAD51, MTRNR2L1, KRT20, WIF1 
       LEP, CTSW, LEFTY2, CLEC4E, CD53, APOB, CCRL2, CUZD1, WNT9A, SCGB3A1 
PC_ 2 
Positive:  HLA-DRB5, HLA-DQB1, ITGB2, LYZ, HLA-DQA1, HLA-DPA1, PTPRCAP, PTPRC, CD68, CXCR5 
       KRT15, CD163, IL10RA, CD52, JAK2, C1QA, FYB1, CD37, CCL5, TNFSF13B 
       MRC1, CD69, ZFP36, IL2RG, ARHGDIB, TNFSF12, BTG1, GZMH, GPR183, NLRC5 
Negative:  MPO, IL17A, PTGES2, LIF, CCRL2, IGHG1, LAIR1, IGHG2, MTRNR2L1, TNFRSF17 
       KRT13, EFNA4, IGKC, IL17D, LPAR5, RPS4Y1, TNFRSF9, PSCA, AZU1, PTGS2 
       EPHB6, WIF1, MZB1, APOB, WNT7B, CD70, TLR2, NRG4, IL20, PTGIS 
PC_ 3 
Positive:  MZB1, XBP1, PLA2R1, TNFRSF13B, DNTT, ATF3, LPAR5, VEGFC, AGR2, CD38 
       PTGDR2, FGF12, IRF4, PROKR1, CAV1, ADORA2A, COL3A1, ARTN, CXCR5, GAS6 
       CCL13, GC, SAA1, ADGRV1, SEC61G, CD27, COL1A1, WNT5A, NRIP3, BGN 
Negative:  C1QB, HLA-DPA1, HLA-DQA1, C1QC, C1QA, PTGES2, S100A4, LIF, CD53, HLA-DQB1 
       HLA-DRB5, EFNA4, KRT13, CCRL2, CD163, STAT5A, ITGB2, MTRNR2L1, TNFRSF9, SELENOP 
       TNFRSF17, LGALS9, CCL5, IL17D, LYZ, CD68, FYB1, WNT7B, CD2, WIF1 
PC_ 4 
Positive:  KRT13, WIF1, TNFRSF17, TNFRSF9, IGHG2, IGHG1, WNT7B, TSLP, MPO, LIF 
       WNT7A, EFNA4, CCRL2, IL17D, PTGES2, FZD6, MZB1, IL17A, PTGDR2, ADGRA3 
       ADGRG5, FGG, MTRNR2L1, STAT5A, GZMH, WNT9A, LAIR1, ST6GAL1, CD5L, IL12A 
Negative:  CSF1R, CLEC4A, CXCL17, RPS4Y1, SMARCB1, TLR2, IL12RB1, FYN, EPHB6, IL20 
       NRG4, NOD2, TWIST1, CCL3, TNFAIP6, LUM, COL15A1, PTGIS, IL15RA, GDF3 
       CD163, CLOCK, RAC2, CD81, PTGS2, NANOG, CTLA4, PLAC8, ACKR3, AZU1 
PC_ 5 
Positive:  COL1A1, COL3A1, COL1A2, MGP, DCN, TAGLN, COL6A2, LUM, CALD1, COL6A3 
       BGN, SELENOP, MMP2, CXCL12, TIMP1, HGF, PDGFRA, CD81, C1QB, C1QC 
       C1QA, CYP1B1, SNAI2, SLC40A1, IGFBP6, MRC2, THBS2, NGFR, BMP5, COL14A1 
Negative:  CD27, FYN, MZB1, XBP1, CCL5, SEC61G, CD38, RAC2, CST7, GAS6 
       GZMA, CD8A, CLOCK, PLAC8, ST6GAL1, NKG7, JCHAIN, PRSS2, MZT2A, FKBP11 
       RPS4Y1, ITGAL, ICOS, DUSP2, DUSP5, IL2RG, IGHA1, HSP90B1, TNFSF14, NOD2 
12:11:31 UMAP embedding parameters a = 0.9922 b = 1.112
12:11:31 Read 1038 rows and found 20 numeric columns
12:11:31 Using Annoy for neighbor search, n_neighbors = 30
12:11:31 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:31 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f353212c37
12:11:31 Searching Annoy index using 1 thread, search_k = 3000
12:11:31 Annoy recall = 100%
12:11:32 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:11:33 Initializing from normalized Laplacian + noise (using RSpectra)
12:11:33 Commencing optimization for 500 epochs, with 40156 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:34 Optimization finished
[1] 2.3
Regressing out log10totalcounts

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  |=============                                                                                                     |  12%Warning in theta.ml(Y, mu, sum(w), w, limit = control$maxit, trace = control$trace >  :
  iteration limit reached
Warning in theta.ml(Y, mu, sum(w), w, limit = control$maxit, trace = control$trace >  :
  iteration limit reached

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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, MZT2A, MALAT1, XBP1, MZB1, TYK2, IFITM1, MGP 
       COL3A1, GPX1, CALD1, HSP90B1, RPL34, C1QA, CD38, CD81, FKBP11, IFI27 
       JCHAIN, C1QC, COL1A1, TAGLN, IGHA1, BST2, CD27, LPAR5, TIMP1, HLA-DRB5 
Negative:  PSCA, IL17D, EFNA4, WNT7B, STAT5A, IL17A, CD70, TNFRSF17, KRT13, LIF 
       SCGB3A1, TCL1A, TWIST2, RAD51, TNFRSF9, KRT20, RARG, SLC2A4, MTRNR2L1, PTGES2 
       LEP, CCRL2, IFNA1, CTSW, WNT9A, TNFSF15, WIF1, CLEC4E, CD53, PROKR1 
PC_ 2 
Positive:  HLA-DRB5, LYZ, ITGB2, HLA-DQB1, HLA-DQA1, PTPRCAP, CD52, HLA-DPA1, CXCR5, JAK2 
       KRT15, PTPRC, IL10RA, GPR183, TNFSF13B, CD68, CD163, CD69, C1QA, NLRC5 
       TNFSF12, GZMH, IL2RG, OAS3, FGG, NKG7, CD48, MRC1, IL2RB, CD37 
Negative:  MPO, LAIR1, PTGES2, IL17A, CCRL2, LIF, MTRNR2L1, KRT13, IL20, TNFRSF17 
       AZU1, IGHG1, EFNA4, RPS4Y1, APOB, IL12RB1, PTGS2, EPHB6, IGHG2, TLR2 
       CD70, LPAR5, NRG4, PSCA, IGKC, WIF1, IL17D, PTGIS, TNFRSF9, ELANE 
PC_ 3 
Positive:  MZB1, XBP1, PLA2R1, TNFRSF13B, AGR2, GAS6, PTGDR2, VEGFC, LPAR5, ATF3 
       DNTT, ARTN, TSLP, CD38, FKBP11, ADORA2A, CAV1, COL3A1, FGF12, UCP1 
       COL1A1, CCL13, WNT7A, ST6GAL1, IRF4, TAGLN, ESR1, CSF2RB, ACTG2, LCN2 
Negative:  C1QB, HLA-DPA1, C1QC, HLA-DQA1, C1QA, ITGB2, HLA-DQB1, HLA-DRB5, CD163, CD53 
       S100A4, LIF, PTGES2, CCL5, EFNA4, LYZ, CD68, CCRL2, STAT5A, LGALS9 
       FYB1, MTRNR2L1, KRT13, SELENOP, CD2, GPX1, TNFRSF9, IL17D, PTGDS, SRGN 
PC_ 4 
Positive:  KRT13, WIF1, TNFRSF9, EFNA4, LIF, TNFRSF17, IGHG2, PTGES2, IGHG1, IL17D 
       WNT7B, CCRL2, IL17A, S100A4, MTRNR2L1, ADGRG5, MPO, TSLP, WNT7A, CD70 
       STAT5A, FGG, FZD6, CXCR6, TCL1A, MMP1, IL12A, TWIST2, LAIR1, GZMH 
Negative:  CSF1R, CLEC4A, CXCL17, FYN, TLR2, RPS4Y1, SMARCB1, TWIST1, NRG4, IL20 
       NOD2, EPHB6, IL12RB1, CTLA4, IL15RA, CCL3, RAC2, NANOG, CLOCK, TNFAIP6 
       LUM, PTGS2, COL15A1, LY6D, RGS1, ALCAM, PLAC8, GDF3, AZU1, CD44 
PC_ 5 
Positive:  CD27, MZB1, CCL5, CD38, XBP1, ST6GAL1, GAS6, CD79A, DUSP5, CST7 
       TNFSF14, FYN, RAC2, IL2RG, GZMA, ICOS, JCHAIN, IGHG2, SEC61G, AZU1 
       PRSS2, FKBP11, IL6R, CD8A, CSF2RB, CFLAR, PTPRCAP, CCR5, CD48, CLOCK 
Negative:  COL3A1, COL1A1, COL1A2, COL6A2, MGP, TAGLN, DCN, LUM, CALD1, BGN 
       COL6A3, CXCL12, TIMP1, CD81, MMP2, SELENOP, PDGFRA, HGF, C1QC, C1QA 
       SNAI2, C1QB, SLC40A1, CYP1B1, TLR4, HDAC4, COL14A1, CD163, RSPO2, PTGDS 
12:11:45 UMAP embedding parameters a = 0.9922 b = 1.112
12:11:45 Read 704 rows and found 20 numeric columns
12:11:45 Using Annoy for neighbor search, n_neighbors = 30
12:11:45 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:45 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f36b925262
12:11:45 Searching Annoy index using 1 thread, search_k = 3000
12:11:45 Annoy recall = 100%
12:11:46 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:11:47 Initializing from normalized Laplacian + noise (using RSpectra)
12:11:47 Commencing optimization for 500 epochs, with 26686 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:48 Optimization finished
[1] 2.4
Regressing out log10totalcounts

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  iteration limit reached
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Warning in theta.ml(Y, mu, sum(w), w, limit = control$maxit, trace = control$trace >  :
  iteration limit reached
Warning in sqrt(1/i) : NaNs produced

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Warning in theta.ml(Y, mu, sum(w), w, limit = control$maxit, trace = control$trace >  :
  iteration limit reached

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  iteration limit reached
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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG1, IGHG2, MZT2A, MALAT1, XBP1, MZB1, TYK2, MGP, IFITM1 
       CALD1, RPL34, HSP90B1, GPX1, COL3A1, FKBP11, C1QA, CD81, CD38, COL1A1 
       C1QC, JCHAIN, TAGLN, LPAR5, IFI27, IGHA1, BST2, CD27, HLA-DRB5, TIMP1 
Negative:  PSCA, CD70, IL17D, EFNA4, SCGB3A1, STAT5A, CLEC4E, TCL1A, SLC2A4, RARG 
       RAD51, TNFRSF17, WNT7B, IL17A, KRT20, CIDEA, KRT13, DDR2, LEP, TNFSF15 
       LIF, ADGRA3, WNT9A, TWIST2, PROKR1, HDAC3, QRFPR, STAT4, CLEC4A, ATG5 
PC_ 2 
Positive:  HLA-DQA1, LYZ, ITGB2, KRT15, HLA-DRB5, WNT7A, JAK2, PTPRCAP, HLA-DQB1, CXCR5 
       PTPRC, CD69, C1QA, GZMH, NKG7, GZMK, OAS3, CASP8, HLA-DPA1, IL2RG 
       IL10RA, TNFRSF18, FGG, CST7, TGFB1, OASL, IL2RB, CD163, VHL, OAS1 
Negative:  RPS4Y1, MPO, AZU1, CLEC4A, IL20, EPHB6, SMARCB1, LAIR1, PTGIS, TLR2 
       NRG4, CXCL17, CCRL2, PTGS2, ADGRF4, IL12RB1, PTGES2, CSF1R, NOD2, SOSTDC1 
       APOB, NANOG, KRT86, CTLA4, IL17D, CLOCK, LPAR5, ANGPT2, COL5A1, WNT5A 
PC_ 3 
Positive:  HLA-DPA1, C1QB, HLA-DQA1, HLA-DQB1, C1QC, ITGB2, LIF, C1QA, HLA-DRB5, CD163 
       LYZ, CCL5, S100A4, CD53, CCRL2, LGALS9, EFNA4, STAT5A, CD68, FYB1 
       PTGES2, CD3E, TNFRSF9, GPX1, CD2, FYN, IL17D, MTRNR2L1, SRGN, CSF1R 
Negative:  MZB1, XBP1, COL3A1, TNFRSF13B, TSLP, FGF12, WNT7A, PTGDR2, BGN, PLA2R1 
       ATF3, COL1A1, TAGLN, ARTN, RSPO2, VEGFC, CALD1, MGP, EFNB3, GAS6 
       DNTT, TNFSF9, CCL28, FKBP11, SAA1, IRF4, ATM, TNFSF13B, LPAR5, DMBT1 
PC_ 4 
Positive:  IGHG2, IGHG1, DUSP5, WIF1, GZMA, CCL5, GZMK, PTPRCAP, CD8A, TNFRSF17 
       MPO, CCRL2, CXCR6, CCR5, CD79A, CD47, CD48, TNFSF14, COL9A2, ST6GAL1 
       IL17A, ITGAL, XBP1, ATG12, TCL1A, MTRNR2L1, CD3E, IL2RG, NKG7, KRT13 
Negative:  COL3A1, MGP, TAGLN, COL1A1, LUM, COL1A2, CALD1, CD81, C1QC, TIMP1 
       COL6A2, CD163, C1QA, PDGFRA, TLR4, HGF, BGN, MMP2, IFI27, DCN 
       CSF1R, C1QB, CD68, SRGN, CLEC7A, IFNGR1, MS4A4A, IFITM1, GPX1, CMKLR1 
PC_ 5 
Positive:  TLR2, CSF1R, CXCL17, NOD2, FYN, PLAC8, CCL3, CLEC4A, CUZD1, IL12RB1 
       PRSS2, CLOCK, RAC2, IL15RA, CST7, PTGS2, IGHM, CXCR4, IL3RA, KRT1 
       TAP1, GDF3, IL20, AZU1, RGS1, IL6, TWIST1, RPS4Y1, TNFAIP6, ATM 
Negative:  SELENOP, DCN, KRT13, EFNA4, PTGES2, COL6A2, CCRL2, TNFRSF9, S100A4, COL1A2 
       MGP, WIF1, COL1A1, WNT7A, COL6A3, COL3A1, SNAI2, LIF, CXCL12, TCL1A 
       TAGLN, IL17D, TWIST2, MTRNR2L1, FGG, C1QB, BGN, CIDEA, CD70, WNT7B 
12:11:56 UMAP embedding parameters a = 0.9922 b = 1.112
12:11:56 Read 420 rows and found 20 numeric columns
12:11:56 Using Annoy for neighbor search, n_neighbors = 30
12:11:56 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:56 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f35753f9b6
12:11:56 Searching Annoy index using 1 thread, search_k = 3000
12:11:56 Annoy recall = 100%
12:11:57 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:11:58 Initializing from normalized Laplacian + noise (using RSpectra)
12:11:58 Commencing optimization for 500 epochs, with 15338 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:11:59 Optimization finished
[1] 2.5
Regressing out log10totalcounts

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Warning in theta.ml(Y, mu, sum(w), w, limit = control$maxit, trace = control$trace >  :
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Warning in glm.nb(formula = fmla, data = regression.mat) :
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Centering and scaling data matrix

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PC_ 1 
Positive:  IGKC, IGHG2, IGHG1, MZT2A, MALAT1, XBP1, MZB1, TYK2, IFITM1, GPX1 
       HSP90B1, FKBP11, COL3A1, CALD1, MGP, RPL34, C1QA, CD81, C1QC, COL1A1 
       TAGLN, CD38, LPAR5, JCHAIN, IFI27, IGHA1, HLA-DRB5, HLA-DPA1, TIMP1, ITGB2 
Negative:  PSCA, CD70, EFNA4, IL17D, RAD51, DDR2, SCGB3A1, TCL1A, TNFRSF17, HDAC3 
       STAT5A, CIDEA, CLEC4E, CSF3R, KRT20, SLC2A4, FGG, QRFPR, IL12A, CLEC4A 
       LEP, WNT7B, TWIST2, RARG, CUZD1, NRG4, IL17A, KRT13, STAT4, LIF 
PC_ 2 
Positive:  PTGIS, RPS4Y1, PTGES2, EPHB6, IL20, NRG4, AZU1, MPO, CXCL17, CCRL2 
       TLR2, EFNA4, ST6GALNAC3, ADGRF4, IL12RB1, IL17D, NOD2, SMARCB1, G6PC2, LAIR1 
       ANGPT2, IL33, KRT86, DNMT1, CLEC4A, RPL32, COL5A1, CSF1R, LAMP3, CD79A 
Negative:  WNT7A, KRT15, JAK2, TNFSF9, FGG, CXCR5, CD80, NLRP3, ZFP36, CD5L 
       TNFSF13B, VEGFC, MMP1, ADGRG3, ATF3, GZMH, NPPC, PTGDR2, TNFRSF13B, OAS1 
       VHL, FGF12, TNFSF18, TLR7, PTPRCAP, MRC1, CASP8, FOXP3, RELT, CHGA 
PC_ 3 
Positive:  MZB1, TSLP, TAGLN, XBP1, PLA2R1, IGHG2, ATF3, COL3A1, IGKC, AGR2 
       WNT7A, COL1A1, MPO, LPAR5, RSPO2, TNFRSF13B, IGHG1, COL6A3, LUM, DMBT1 
       ARTN, FGG, ADGRL1, EFNB3, DCN, ESR1, SLPI, ADGRB2, UCP1, CALD1 
Negative:  HLA-DPA1, ITGB2, HLA-DQB1, CD2, HLA-DQA1, HLA-DRB5, CCL5, FYB1, CD163, CD3E 
       LYZ, C1QC, CLEC2D, CCL19, CD68, CSK, IL16, CD44, MZT2A, CST7 
       NLRC5, KLRK1, FYN, C1QA, PTPRCAP, TYK2, GZMK, CXCR4, BTG1, C1QB 
PC_ 4 
Positive:  CXCR6, WIF1, KRT13, EFNA4, CCRL2, S100A4, TNFRSF9, LIF, SELENOP, MTRNR2L1 
       STAT5A, IL17D, PTGES2, TWIST2, TNFRSF17, FGF7, TCL1A, PSCA, C1QB, WNT7B 
       IL12A, LGALS9, CD70, CLEC4D, IL17A, TGFB1, RARG, CLEC12A, CPA3, SNAI2 
Negative:  CSF1R, TWIST1, TLR2, NOD2, APOA1, KRT4, CLEC4A, IFI27, KRT20, CXCL17 
       ITGAM, SELL, PLAC8, IL15RA, CUZD1, CSK, G6PC2, RAC2, ATM, GPBAR1 
       TNFAIP6, CSF2RA, IFITM1, MERTK, FFAR3, ACKR1, FCRLA, TNFSF15, RGS2, GC 
PC_ 5 
Positive:  COL3A1, MGP, COL1A1, COL1A2, COL6A2, LUM, TAGLN, CALD1, C1QC, DCN 
       BGN, TIMP1, C1QA, MMP2, SELENOP, COL6A3, C1QB, CD163, MMP19, HGF 
       PDGFRA, SRGN, CLEC7A, CD81, TLR4, NLRP3, CXCL12, CD68, DHRS2, CMKLR1 
Negative:  IL2RG, IGHG2, IGHG1, DUSP5, ST6GAL1, ADGRV1, PTPRCAP, FYN, CD38, GDF3 
       PDCD1, AZU1, NLRC5, CD52, CLOCK, TLR2, GZMK, ATG12, ANGPT2, UBE2C 
       RAC2, GDNF, NOD2, CD28, CHEK2, UCP1, TOX, ITGAL, CD48, GAS6 
12:12:04 UMAP embedding parameters a = 0.9922 b = 1.112
12:12:04 Read 218 rows and found 20 numeric columns
12:12:04 Using Annoy for neighbor search, n_neighbors = 30
12:12:04 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:12:04 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f37a40314e
12:12:04 Searching Annoy index using 1 thread, search_k = 3000
12:12:04 Annoy recall = 100%
12:12:05 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:12:06 Initializing from normalized Laplacian + noise (using RSpectra)
12:12:06 Commencing optimization for 500 epochs, with 7832 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:12:06 Optimization finished
[[1]]

[[2]]

[[3]]

[[4]]

[[5]]

[[6]]

[[7]]

[[8]]

[[9]]

[[10]]

[[11]]

cells with > 80 RNA counts seem to do best

Plot UMAP

#filter by ncounts
bcell_seurat_fil <- subset(bcell_seurat, subset = log10totalcounts > 1.9)

#run UMAP
bcell_seurat_fil <- RunPCA(bcell_seurat_fil, features = bcell_all.genes, npcs=20)
PC_ 1 
Positive:  MARCO, CCL7, CLEC4D, MMP3, RSPO2, IL36G, FOXP3, GDNF, MMP1, GPER1 
       LY75, IFNL3, IFNG, ACKR1, CAMP, NLRC4, PGF, IAPP, CYP19A1, INHBB 
       EFNB3, VPREB3, IGHA1, ADGRV1, ADGRB3, KRT5, CD8B, COL5A2, KRT6B, CHGA 
Negative:  CD53, S100A4, STAT5A, IL17D, PTGES2, TNFRSF17, LIF, IL16, SELENOP, LAIR1 
       LGALS9, MPO, WNT7B, CD70, BTG1, RPL32, WIF1, IL15RA, TNFRSF9, PSCA 
       MKI67, TYROBP, CD28, CCRL2, EFNA4, MTRNR2L1, CYTOR, RAC2, ARHGDIB, IL17A 
PC_ 2 
Positive:  PSCA, KRT13, LIF, IL17D, IL17A, WNT7B, EFNA4, TNFRSF9, CCRL2, TNFRSF17 
       STAT5A, PTGES2, CD70, MTRNR2L1, APOB, WIF1, LEP, TWIST2, KRT86, KRT20 
       CUZD1, ADGRF4, RAD51, GDF3, MPO, IL20, OLR1, LEFTY2, SLC2A4, ELANE 
Negative:  XBP1, COL3A1, IFI27, MZB1, GPX1, MGP, IFITM1, C1QA, CD81, C1QC 
       CALD1, CD38, RPL34, TAGLN, JCHAIN, CD163, BST2, HLA-DRB5, MALAT1, CD27 
       HSP90B1, COL1A1, IGKC, ITGB2, FKBP11, CXCR4, SRGN, TIMP1, TYK2, HMGB2 
PC_ 3 
Positive:  SERPINB5, PROKR1, ATF3, DNTT, VEGFC, TNFRSF13B, CXCR5, NLRP2, NRIP3, ACTG2 
       FGG, CCL13, MMP3, TNFSF13B, WNT5B, BMP6, CCL28, GC, AATK, ADORA2A 
       EFNB3, FGF12, GDNF, AGR2, DMBT1, ADGRV1, TCL1A, LINC02446, COL9A3, SLC2A4 
Negative:  LIF, KRT13, PTGES2, CCRL2, S100A4, C1QB, STAT5A, TNFRSF17, TNFRSF9, MTRNR2L1 
       CD53, EFNA4, IL17A, IL17D, MPO, WNT7B, LGALS9, HLA-DQA1, SELENOP, WIF1 
       CD70, C1QA, HLA-DPA1, C1QC, LAIR1, PSCA, ITGB2, CD163, CCL5, HLA-DRB5 
PC_ 4 
Positive:  CCL5, GZMK, PTPRCAP, HLA-DQA1, FYB1, NKG7, CD52, HLA-DPA1, HLA-DQB1, LYZ 
       CD84, CD2, CD3E, ITGB2, NLRC5, CD69, CST7, PRF1, GZMH, PDCD1 
       PTPRC, CD37, KLRK1, GZMB, OASL, IL16, CD44, IL2RG, LAG3, IL2RB 
Negative:  MZB1, XBP1, COL3A1, TLR2, LPAR5, IGKC, RPS4Y1, MGP, PTGS2, TAGLN 
       COL1A1, JCHAIN, IGHG2, CD38, COL5A1, IGHG1, LUM, SMARCB1, TNFAIP6, CLEC4A 
       HSP90B1, EPHB6, BGN, WNT5A, CALD1, HGF, COL1A2, NRG4, CXCL17, MPO 
PC_ 5 
Positive:  KRT13, TSLP, TNFRSF17, PTGDR2, MPO, WIF1, WNT7B, LIF, VEGFC, WNT7A 
       IL17D, XBP1, TNFRSF9, COL1A1, STAT5A, COL3A1, MZB1, MMP1, SNAI2, EFNA4 
       ADGRA3, FZD6, TAGLN, NRIP3, COL1A2, IL17A, DMBT1, CD5L, IGHG2, LAIR1 
Negative:  CLEC4A, FYN, IL12RB1, CSF1R, RPS4Y1, NRG4, SMARCB1, CXCL17, EPHB6, GDF3 
       NOD2, TWIST1, IL20, CCL5, CCL3, ACKR3, TLR2, TNFAIP6, PLAC8, CTLA4 
       PTGIS, CLOCK, CD2, RAC2, RGS1, AZU1, COL15A1, CXCR4, IL7R, FYB1 
bcell_seurat_fil <- RunUMAP(bcell_seurat_fil, dims = 1:20)
12:12:08 UMAP embedding parameters a = 0.9922 b = 1.112
12:12:08 Read 2040 rows and found 20 numeric columns
12:12:08 Using Annoy for neighbor search, n_neighbors = 30
12:12:08 Building Annoy index with metric = cosine, n_trees = 50
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:12:09 Writing NN index file to temp file /tmp/RtmpbjSzLh/file4d5f36da3b31d
12:12:09 Searching Annoy index using 1 thread, search_k = 3000
12:12:09 Annoy recall = 100%
12:12:10 Commencing smooth kNN distance calibration using 1 thread with target n_neighbors = 30
12:12:11 Initializing from normalized Laplacian + noise (using RSpectra)
12:12:11 Commencing optimization for 500 epochs, with 85384 positive edges
Using method 'umap'
0%   10   20   30   40   50   60   70   80   90   100%
[----|----|----|----|----|----|----|----|----|----|
**************************************************|
12:12:13 Optimization finished
Idents(object = bcell_seurat_fil) <- bcell_seurat_fil@meta.data$'bcell_subclust' 

# remove old UMAP cols from metadata
bcell_seurat_fil@meta.data <- bcell_seurat_fil@meta.data[,which(!(colnames(bcell_seurat_fil@meta.data) %in% c('UMAP_1', 'UMAP_2')))]

# Add new UMAP cols
bcell_seurat_fil <- AddMetaData(bcell_seurat_fil,
                  data.frame(bcell_seurat_fil@reductions$umap@cell.embeddings))


# Make sure it's not too batchy
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=tissuename)) +
  geom_point(size=1) +
  facet_wrap(~tissuename) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())


# Plot
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=bcell_subclust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())

ggsave(file = 'figures/bcellsubclust_UMAP.svg',
       width = 4,
       height = 3,
       device = svg)



# Plot plasmablast and B-cell identity
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=clust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols,
                    guide = guide_legend(title = "Patrick\ncell types",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())

ggsave(file = 'figures/bcellPlasma_UMAP.svg',
       width = 4,
       height = 3,
       device = svg)

NA
NA

Subcluster vs other variables

Continuous variables

## define continuous variables
contvars <- list("totalcounts", "Area", "Mean.PanCK", "Max.PanCK", "Mean.CD45", "Max.CD45", "Mean.DAPI", "Max.DAPI")


## B-cells
# MLE-cell vs continuous variables
plts <- lapply(contvars, function(d) {
  ggplot(bcell_seurat@meta.data,
         aes_string(x = "bcell_subclust",
                    y = d)) + geom_violin() +
    geom_jitter(size = 0.5, alpha = 0.1) +
    scale_y_continuous(trans='log10')
  
})
Warning: `aes_string()` was deprecated in ggplot2 3.0.0.
ℹ Please use tidy evaluation idioms with `aes()`.
ℹ See also `vignette("ggplot2-in-packages")` for more information.
This warning is displayed once every 8 hours.
Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.
plts <- ggarrange(plotlist=plts, labels = contvars, common.legend = F)
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 17 rows containing non-finite outside the scale range (`stat_ydensity()`).
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 2 rows containing non-finite outside the scale range (`stat_ydensity()`).
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 79 rows containing non-finite outside the scale range (`stat_ydensity()`).
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 26 rows containing non-finite outside the scale range (`stat_ydensity()`).
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 15 rows containing non-finite outside the scale range (`stat_ydensity()`).
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning in scale_y_continuous(trans = "log10") :
  log-10 transformation introduced infinite values.
Warning: Removed 10 rows containing non-finite outside the scale range (`stat_ydensity()`).
ggsave(filename = 'figures/bcell_MLEcellsubclusts_contvar_metadats.png',
       plts,
       width = 20,
       height = 14)

Discrete variables

## Define discrete variables
discvars <- list("tissuename", "class", "clust", 'context', 'position.vs.glom')

## B-cells
plts <- lapply(discvars, function(d) {
  ggplot(bcell_seurat@meta.data,
         aes_string(x = "bcell_subclust", fill = d)) +
    geom_bar()
  
})

plts <- ggarrange(plotlist=plts,
                  labels = discvars, 
                  common.legend = F)

ggsave(filename = 'figures/bcell_MLEcell_discvar_metadats.png',
       plts,
       width = 20,
       height = 15)

Lupus class

# B-cells
## look at over-representation of clusters in each class
bcell_unsup_lupusclass_chisq <- chisq.test(table(bcell_seurat@meta.data$class,
                                                 bcell_seurat@meta.data$bcell_subclust))
Warning in chisq.test(table(bcell_seurat@meta.data$class, bcell_seurat@meta.data$bcell_subclust)) :
  Chi-squared approximation may be incorrect
bcell_unsup_lupusclass_chisq_res <- melt(bcell_unsup_lupusclass_chisq$residuals)
colnames(bcell_unsup_lupusclass_chisq_res) <- c('class',
                                                'cluster',
                                                'residual')

bcell_unsup_lupusclass_chisq_res %>% 
  arrange(plyr::desc(residual))

## most over-represented cell subset in each cluster, along with residual
bcell_unsup_class_overrep <- bcell_unsup_lupusclass_chisq_res %>%
  group_by(cluster) %>%
  slice_max(n=1, order_by=residual) %>%
  summarize(cluster=cluster, class=class, max_residual=residual, )

## plot class vs cluster with underlying plot of the class most over-represented and its chi-sq residual
## Most interesting are c, e, h, m, and t (residuals > 5)
ggplot() +
  geom_bar(data=bcell_seurat@meta.data,
           color="black",
           aes(x=bcell_subclust,
               fill=class)) +
  geom_point(data=bcell_unsup_class_overrep,
             color="black",
             shape=21,
             aes(x=cluster,
                 y=-30,
                 fill=class,
                 size=max_residual)) +
  labs(title = 'B-cell Subcluster Prevalence across Lupus Nephritis Classes') +
  ylab('Number of cells') +
  xlab('B-cell subluster ID') +
  guides(fill=guide_legend(title="LN Class"),
         size=guide_legend(title='ChiSq Residual'))

ggsave('figures/bcell_subclusterIDvsLNClass.png')
Saving 7.29 x 4.5 in image
# ok, screw that. Let's do a diseased vs undiseased test first instead
bcell_seurat@meta.data$disease = 'LN'
bcell_seurat@meta.data[which(bcell_seurat@meta.data$class == 'control'),'disease'] <- 'Control'

bcell_subclust_chisq_dz <- bind_rows(lapply(new, function(cl) {
  print(cl)
  df <- bcell_seurat@meta.data
  df$cl <- cl
  df$cl <- as.character(df$cl)
  df[which(df$bcell_subclust != cl),'cl'] <- 'other clusters'
  chisq <- chisq.test(table(df$disease, df$cl))
  return(cbind(data.frame(subcluster = cl), broom::tidy(chisq)))
  
  
}))
[1] B.4
Levels: B.1 B.2 B.3 B.4
[1] B.1
Levels: B.1 B.2 B.3 B.4
Warning in chisq.test(table(df$disease, df$cl)) :
  Chi-squared approximation may be incorrect
[1] B.3
Levels: B.1 B.2 B.3 B.4
[1] B.2
Levels: B.1 B.2 B.3 B.4
bcell_subclust_chisq_dz$p.value.adj = p.adjust(bcell_subclust_chisq_dz$p.value,
                                               method = 'BH')

fig <- ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(y = disease,
               fill = bcell_subclust),
           position = 'fill',
           color = 'black') +
  geom_point(data = data.frame(x=c(0.15, 0.69),
                               y=c('control','sle')),
             aes(x=x,y=y),
             shape=8) +
  scale_fill_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  scale_x_continuous(labels = scales::percent) +
  ylab(label = element_blank()) +
  xlab(label = element_blank())


ggsave(filename = 'figures/bcell_subclust_lupusclass.svg',
       plot = fig,
       width = 3,
       height = 1,
       units = "in",
       device = svg)


bcell_subclust_chisq_dz
NA

Tubulointerstitial hotspots

context <- readRDS('processed_data/context4.RDS')
context <- annot[,c('cell_ID', 'context')]
#bcell_seurat@meta.data <- merge(bcell_seurat@meta.data, context, by = 'cell_ID')

df <- melt(table(bcell_seurat@meta.data[,#which(bcell_seurat@meta.data$disease == 'LN'),
                             c('context', 'bcell_subclust', 'disease')]))

# Get the percentage of B.3 cells in hotspots, and overall
all_cell_perc <- df %>% group_by(bcell_subclust) %>% summarize(sum(value)/sum(df$value))
hotspot_perc <- subset(df, context == 'hotspot') %>% group_by(bcell_subclust) %>% summarize(sum(value) / sum(df[which(df$context == 'hotspot'),'value']))

# perform a chisq
chisqtable <- table(data.frame(
  B.3 = sapply(bcell_seurat@meta.data$bcell_subclust, function(c) {c=='B.3'}),
  hotspot = sapply(bcell_seurat@meta.data$context, function(c) {c=='hotspot'})))
chisq.test(chisqtable,
              )

    Pearson's Chi-squared test with Yates' continuity correction

data:  chisqtable
X-squared = 133.67, df = 1, p-value < 2.2e-16
fig <- ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(y = bcell_subclust,
               fill = context),
           position = 'fill',
           color = 'black') +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  scale_x_continuous(labels = scales::percent) +
  ylab(label = 'B-cell\nSubcluster') +
  xlab(label = element_blank()) +
  labs(fill = "Location") +
  theme(legend.position = "bottom",
        legend.key.size = unit(0.3, "cm"),
        legend.margin = margin(t = -0.5, unit = "cm"),
        legend.title = element_text(size = 10)) +
  guides(fill = guide_legend(title.position = 'top',
                             nrow = 4))

ggsave(filename = 'figures/bcell_subclust_hotspots.svg',
       plot = fig,
       width = 2,
       height = 2,
       units = "in",
       device = svg)

Subcluster DEGs

Identify marker genes


# B-cells
# set identity of cells for finding markers to the clusters discovered with MLEcell
Idents(object = bcell_seurat) <- bcell_seurat@meta.data$'bcell_subclust' 

bcell_MLE_markers <- FindAllMarkers(bcell_seurat,
                                    only.pos = TRUE,
                                    min.pct = 0.25,
                                    logfc.threshold = 0.25)
Calculating cluster B.1
For a more efficient implementation of the Wilcoxon Rank Sum Test,
(default method for FindMarkers) please install the limma package
--------------------------------------------
install.packages('BiocManager')
BiocManager::install('limma')
--------------------------------------------
After installation of limma, Seurat will automatically use the more 
efficient implementation (no further action necessary).
This message will be shown once per session

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bcell_MLE_markers <-  merge(bcell_MLE_markers, 
                                data.frame(contam[,c("B-cell", "plasmablast")]), 
                            by.x = 'gene',
                            by.y = 'row.names',
                            all.x=T)

# Retrive top statistically significant markers
bcell_MLE_markers_top5 <- bcell_MLE_markers %>%
  filter(p_val_adj < 0.01) %>%
    group_by(cluster) %>%
    slice_max(n = 5, order_by = avg_log2FC)

# Plot the cluster and the top three markers on UMAP, with an additional label showing the top 5 genes with genes affected by contamination in RED
for(cl in unique(bcell_MLE_markers_top5$cluster)) {
  
  df <- bcell_MLE_markers_top5 %>%
    filter(cluster == cl) %>%
    arrange(desc(avg_log2FC))

  plts <-lapply(df$gene, function(x) {
    FeaturePlot(bcell_seurat_fil, x, max.cutoff="q99", pt.size=0.2) + ggtitle(x)
  })
  
  dat <- bcell_seurat_fil@meta.data
  dat$alp_cluster <- sapply(dat$bcell_subclust,
                            function(x){
                              if(x==cl){
                                return(1)} else {
                                  return(0.2)
                              }})
  col_ref_table <- data.frame(bcell_subclust = new,
                              clust_color = bcellcols[1:length(new)])
  col_ref_table$clust_color <- apply(col_ref_table,
                                     1,
                                     function(x){
                                        if(x[1]==cl) {
                                          return(x[2])
                                        } else {
                                          return('#9E9E9E')
                                        }
                                      })
                              
  
  p4 <- ggplot(dat,
               aes(x=UMAP_1,
                   y=UMAP_2,
                color=bcell_subclust,
                alpha=alp_cluster)) +
  geom_point(size=0.2) +
  scale_color_manual(values=col_ref_table$clust_color) +
  theme(legend.position="none",
        plot.margin= margin(0.5,6,0.5,0.5,unit='cm'))
  
  
  df$pval_adj <- sapply(df$p_val_adj, function(x) sprintf("%.2e", x))
  df$log2FC <- sapply(df$avg_log2FC, function(x) round(x, digits = 2))
    
  p5 <- gridExtra::tableGrob(df[,c('gene',
                                   'p_val_adj',
                                   'log2FC',
                                   'pct.1',
                                   'pct.2'
                                   )])
  
  
  if(length(plts)==1) {G1 <- (plts[[1]] | plot_spacer() | plot_spacer()) / (p4|p5|plot_spacer()) } else 
    if(length(plts)==2) {G1 <- (plts[[1]] | plts[[2]] | plot_spacer()) / (p4|p5|plot_spacer()) } else
      {G1 <- (plts[[1]] | plts[[2]] | plts[[3]]) / (p4|p5|plot_spacer()) }
  
  ggsave(paste0('figures/bcell_subclust_',cl,'_markergenes.png',
                                  sep=""),
         G1,
         width=10,
         height=5,
         units='in')
}

write.csv(bcell_MLE_markers, paste0('bcell_MLE_markers.csv'))

DEGs of interest

goi <- c('IGHM', 'IGHA1', 'IGHG1', 'XBP1', 'HLA-DQA1', 'HLA-DPA1')

# Make a list of feature plots
figs <- lapply(goi, function(g) {
  FeaturePlot(bcell_seurat_fil,
                   features = g,
              pt.size = 0.1,
              max.cutoff = 'q95') + 
    ## add my theme
    my_theme +
    ## make it publication ready
    theme(
      axis.text.x = element_blank(),
      axis.text.y = element_blank(),
      axis.title.x = element_blank(),
      axis.title.y = element_blank(),
      plot.title = element_text(face = "italic",
                                size = 10),
      axis.ticks = element_blank(),
      legend.position = "none"
)})

# Put feature plots together
faceted_plot <- wrap_plots(plotlist = figs,
                           ncol = 2)

# Plot it
ggsave(filename = 'figures/bcell_subclust_goi.svg',
       plot = faceted_plot,
       width = 2.5,
       height = 4,
       units = "in",
       device = svg)

Lupus vs control analyses

Number of cells

df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease) %>%
  summarize(number_bcells = n())
`summarise()` has grouped output by 'tissue'. You can override using the `.groups` argument.
wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_bcells']),
            unlist(df[which(df$disease == 'LN'), 'number_bcells']),
            alternative = 'less')

    Wilcoxon rank sum exact test

data:  unlist(df[which(df$disease == "Control"), "number_bcells"]) and unlist(df[which(df$disease == "LN"), "number_bcells"])
W = 0, p-value = 0.00202
alternative hypothesis: true location shift is less than 0
ggplot(df,
       aes(x = disease,
           y = number_bcells,
           fill = disease)) +
  geom_boxplot(outlier.shape = NA) +
  geom_jitter() +
  scale_fill_manual(values = c('#0571b0', '#ca0020')) +
  ylab('Number of B-cells') +
  xlab(label = element_blank()) +
  theme(legend.position='none')

ggsave(file = 'figures/lupuscontrols_numbcells.svg',
       width = 1.5,
       height = 1.5,
       device = svg)

NA
NA

Number of each subcluster

df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease, bcell_subclust) %>%
  summarize(number_cells = n())
`summarise()` has grouped output by 'tissue', 'disease'. You can override using the `.groups` argument.
lapply(unique(df$bcell_subclust), function(cl) {
  df <- df[which(df$bcell_subclust == cl),]
  wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_cells']),
            unlist(df[which(df$disease == 'LN'), 'number_cells']))
})
Warning in wilcox.test.default(unlist(df[which(df$disease == "Control"),  :
  cannot compute exact p-value with ties
Warning in wilcox.test.default(unlist(df[which(df$disease == "Control"),  :
  cannot compute exact p-value with ties
Warning in wilcox.test.default(unlist(df[which(df$disease == "Control"),  :
  cannot compute exact p-value with ties
[[1]]

    Wilcoxon rank sum test with continuity correction

data:  unlist(df[which(df$disease == "Control"), "number_cells"]) and unlist(df[which(df$disease == "LN"), "number_cells"])
W = 0, p-value = 0.01863
alternative hypothesis: true location shift is not equal to 0


[[2]]

    Wilcoxon rank sum exact test

data:  unlist(df[which(df$disease == "Control"), "number_cells"]) and unlist(df[which(df$disease == "LN"), "number_cells"])
W = 0, p-value = 0.00404
alternative hypothesis: true location shift is not equal to 0


[[3]]

    Wilcoxon rank sum test with continuity correction

data:  unlist(df[which(df$disease == "Control"), "number_cells"]) and unlist(df[which(df$disease == "LN"), "number_cells"])
W = 1, p-value = 0.0317
alternative hypothesis: true location shift is not equal to 0


[[4]]

    Wilcoxon rank sum test with continuity correction

data:  unlist(df[which(df$disease == "Control"), "number_cells"]) and unlist(df[which(df$disease == "LN"), "number_cells"])
W = 0, p-value = 0.01837
alternative hypothesis: true location shift is not equal to 0
ggplot(df,
       aes(x = disease,
           y = number_cells,
           fill = disease)) +
  geom_boxplot(outlier.shape = NA) +
  geom_jitter(width = 0.15) +
  scale_fill_manual(values = c('#0571b0', '#ca0020')) +
  facet_wrap(~bcell_subclust) +
  ylab('Number of B-cells') +
  xlab(label = element_blank()) +
  theme(legend.position='none')

ggsave(file = 'figures/lupuscontrols_numbcells_subclust.svg',
       width = 3.5,
       height = 3.5,
       device = svg)

NA
NA

Proportion of each subcluster

bcell_seurat@meta.data <- bcell_seurat@meta.data[,which(
  !(duplicated(colnames(bcell_seurat@meta.data)))
)]

df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease, bcell_unsup.clust) %>%
  summarize(number_cells = n()) %>%
  mutate(freq = number_cells/sum(number_cells))
`summarise()` has grouped output by 'tissue', 'disease'. You can override using the `.groups` argument.
wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_cells']),
            unlist(df[which(df$disease == 'LN'), 'number_cells']))
Warning in wilcox.test.default(unlist(df[which(df$disease == "Control"),  :
  cannot compute exact p-value with ties

    Wilcoxon rank sum test with continuity correction

data:  unlist(df[which(df$disease == "Control"), "number_cells"]) and unlist(df[which(df$disease == "LN"), "number_cells"])
W = 6.5, p-value = 4.691e-07
alternative hypothesis: true location shift is not equal to 0
ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(x = disease,
               fill = bcell_subclust),
           position = 'fill',
           color = 'black') +
  geom_point(data = data.frame(y=c(0.15, 0.70),
                               x=c('Control', 'LN')),
             aes(x=x,y=y),
             shape=8) +
  scale_fill_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  scale_y_continuous(labels = scales::percent) +
  ylab(label = element_blank()) +
  xlab(label = element_blank())
  

ggsave(file = 'figures/lupuscontrols_propsubclusts.svg',
       width = 2.5,
       height = 3,
       device = svg)

Visual analyses

Load data for visual analyses

# load data
xycoords <- customlocs
row.names(xycoords) <- colnames(raw)

# calculate pairwise distance matrices for all immune cells
dists <- sapply(unique(annot$tissue), function(tis) { 
  
  cells = filter(annot, (tissue == tis &
                           !(cell_ID %in% HB_cells) & # remove hemoglobin+ cells from immune cells
                        basictype %in% c('tcell_cd4',
                                         'tcell_cd8',
                                         'bcell',
                                         'mycell'))) %>% dplyr::select(cell_ID) %>% unlist
  return(dist(xycoords[cells,]))
  
  })

Number of cells within 50 cells

TO perform this analysis, each tissue must be assessed independently to prevent too muchy memory from being used.

# define function that retrieves the 50 closest cells for a given set of "cells of interest"
find_closest_cells <- function(distance_matrix,
                               num_closest_cells,
                               cois = subset(annot, basictype == 'bcell')$cell_ID) { 
  
  ## filter for B cells only
  distance_matrix <- sapply(cois, 
                function(c) {
                  usedist::dist_get(distance_matrix,
                                    c,
                                    cells)
                            })
  row.names(distance_matrix) <- cells
                            
  print(dim(distance_matrix))
  cell_names <- row.names(distance_matrix)
  num_cells <- ncol(distance_matrix)
  closest_cells_list <- vector("list", num_cells)
  
  for (i in 1:num_cells) {
    distances <- distance_matrix[,i]
    closest_indices <- order(distances)[1:num_closest_cells]
    
    closest_cell_names <- cell_names[closest_indices]
    closest_cells_list[[i]] <- closest_cell_names
  }
  
  names(closest_cells_list) <- colnames(distance_matrix)
  return(closest_cells_list)
}

# define function that takes a list of cells and counts the number of immune cells
count_imm_cells <- function(cell_list) {
  
  annot_subset <- subset(annot, basictype %in% (c('bcell',
                                                  'mycell',
                                                  'tcell',
                                                  'NKcell')))
  return(sum(sapply(cell_list, function(c) {c %in% annot_subset$cell_ID})))
}

# iterate through each tissue sample to assess the number of immune cells next to each cell
## initialize empty list
tissue_ids <- unique(annot$tissue)
num_tissues <- length(tissue_ids)
tissue_bcell_nimmune_cells <- vector("list", num_tissues)

## iterate through each tissue's xycords:
for(i in 1:num_tissues) {
  print(paste0('Analzying tissue ', tissue_ids[i]))
  ### compute distance matrix
  cells = filter(annot, (tissue == tissue_ids[i]))$cell_ID
  distance_matrix <- dist(xycoords[cells,])
  
  ### get 50 closest cells to each B cell (not counting the cell itself..)
  closest_cells <- find_closest_cells(distance_matrix,
                                      51,
                                      subset(annot,
                                             (basictype == 'bcell' &
                                               tissue == tissue_ids[i]))$cell_ID)  
  rm(distance_matrix)
  gc() # save memory
  ### count number of immune cells in each list of 50
  imm_cell_nums <- lapply(closest_cells, count_imm_cells)
  ### populate the empty list
  tissue_bcell_nimmune_cells[[i]] <- data.frame(cell_ID = names(closest_cells),
                                                n_imm_cells = unlist(imm_cell_nums)-1) # remove one from each to remove self
} 
[1] "Analzying tissue SP17_2566"
[1] 27795   111
[1] "Analzying tissue SP21_213"
[1] 49093  1081
[1] "Analzying tissue SP17_8693"
[1] 18784    78
[1] "Analzying tissue SP18_3323"
[1] 27247    96
[1] "Analzying tissue SP18_8471"
[1] 12926    67
[1] "Analzying tissue SP19_1139"
[1] 60740   275
[1] "Analzying tissue SP19_4061"
[1] 16025   237
[1] "Analzying tissue SP20_642"
[1] 11839   479
[1] "Analzying tissue SP20_1098"
[1] 30671   111
[1] "Analzying tissue SP20_10838"
[1] 33404   323
[1] "Analzying tissue control2"
[1] 77004     7
[1] "Analzying tissue SP17-1782-A5"
[1] 26112     2
[1] "Analzying tissue SP19-5113"
[1] 130220     19
[1] "Analzying tissue SP22-5235-B14"
[1] 10532    11
tissue_bcell_nimmune_cells_df <- bind_rows(tissue_bcell_nimmune_cells)

## plot data, separating controls and SLE patients
### Prep data
tissue_bcell_nimmune_cells_df$imm_hotspot <- as.numeric(tissue_bcell_nimmune_cells_df$n_imm_cells > 0)
tissue_bcell_nimmune_cells_df <- merge(tissue_bcell_nimmune_cells_df, bcell_seurat@meta.data[,c('bcell_subclust', 'disease')], by = 'row.names')


tab <- table(tissue_bcell_nimmune_cells_df[which(tissue_bcell_nimmune_cells_df$disease=='LN'),c('bcell_subclust', 'imm_hotspot')])
tab[,1] / tab[,2]
       B.1        B.2        B.3        B.4 
0.06769231 0.04226705 0.01237113 0.11557789 
### column for whether a cell is in an tubulointerstitial hotspot
df <- tissue_bcell_nimmune_cells_df
df$context <- sapply(df$cell_ID, function(ci) {annot[ci,'context']})
df$tubinst_hotspot <- sapply(df$context, function(c) {c == 'hotspot'})


### save df
write.csv(df, file = "num_imm_wi_50.csv")

### read df
df <- read.csv("num_imm_wi_50.csv", row.names = 1)

### plot data
ggplot(df,
       aes(x = n_imm_cells,
           fill = as.factor(context))) +
  geom_histogram(color = 'black') +
  facet_wrap(disease~ bcell_subclust,
             scales = 'free_y',
             nrow = 2) +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  ylab(label = element_blank()) +
  xlab(label = 'Number of Nearby Immune Cells') +
  labs(fill = "Location") +
  theme(legend.position = "bottom",
        legend.key.size = unit(0.3, "cm"),
        legend.margin = margin(t = 0, unit = "cm"),
        legend.title = element_text(size = 10))
`stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
ggsave(file = 'figures/lupuscontrols_numbimmcells_location_subclust.svg',
       width = 6,
       height = 3.5,
       device = svg)
`stat_bin()` using `bins = 30`. Pick better value with `binwidth`.

Network Analysis

Hypergeometric dists clust

# fit hypergeometric parameters for each cell type for each sample
adj_matrices <- lapply(dists, function(d) { 
  tmp <- annot[which(annot$cell_ID %in% colnames(as.matrix(d))), c('cell_ID', 'clust')]
  annot_list <- tmp$clust
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1))
  }); names(adj_matrices) <- names(dists)


# get parameters for hypergeometric distribution
adj_matrix_hyperparams <- lapply(seq(1, length(adj_matrices)), function(n) {
  print(n)
  ## define the number of cell types within each distance matrix using the annot dataframe
  ### get the cells from the annotation dataframe
  nctypes <- table(annot[which(annot$cell_ID %in% colnames(as.matrix(dists[[n]]))), 'clust'])
  ### reorder the nctypes to be the same as the columns in the dataset
  nctypes <- nctypes[colnames(adj_matrices[[n]])]
  out <- adj_mat_to_hypergeo_params(adj_matrices[[n]],
                       nctypes)
  out$tissue <- names(dists)[n]
  return(out)
}) %>% bind_rows()
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# look at the networks control vs lupus cases
## define control and sle samples
control_samples <- unique(annot[which(annot$class == 'control'),'tissue'])
sle_samples <- unique(annot[which(annot$class != 'control'), 'tissue'])
adj_matrix_hyperparams$disease <- 'control'
adj_matrix_hyperparams[which(adj_matrix_hyperparams$tissue %in% sle_samples),
                       'disease'] <- 'sle'

adj_matrix_hyperparams$ct1.2 <- t(apply(adj_matrix_hyperparams[,c('ct1', 'ct2')],
                                      1,
                                      function(r) {
                                        paste(unlist(r), 
                                              sep = '_')
                                      }))

## do the following to each set of samples:
### (1) sum hypergeometric distribution hyperparameters (m, n, k) and observed edges (x)
### (2) calculate the expected number of edges (expected.edges)
### (3) calculate the fold increase over expected (fold.incr)
### (4) calculate a p-value

sle.v.control.clust <- adj_matrix_hyperparams %>% 
  dplyr::group_by(ct1, ct2, disease) %>%
  summarise(m = sum(m),
            n = sum(n),
            k = sum(k),
            x = sum(x),
            expected.edges = max(c(qhyper(p=0.5,
                                          m = sum(m),
                                          k = sum(k),
                                          n = sum(n)),
                                   0.5)),
            p.val = max(c(phyper(q=sum(x),
                                 m=sum(m),
                                 k=sum(k),
                                 n=sum(n),
                                 lower.tail = F,
                                 log.p = F),
                          1e-30)))
`summarise()` has grouped output by 'ct1', 'ct2'. You can override using the `.groups` argument.
# add log2FC of observed over expected
sle.v.control.clust$log2.o.e <- log2(sle.v.control.clust$x/sle.v.control.clust$expected.edges)

## adjust p-value for sle and controls separately
### sle
sle <- sle.v.control.clust[which(sle.v.control.clust$disease == 'sle'),]
sle$p.adj <- p.adjust(sle$p.val,
                      method = 'BH')
### control
ctrl <- sle.v.control.clust[which(sle.v.control.clust$disease == 'control'),]            
ctrl$p.adj <- p.adjust(ctrl$p.val,
                      method = 'BH')


# plot the results
## make a key of abbreviated names
key_df <- t(data.frame(c('B-cell', "Bc"),
                     c("plasmablast", "PC"),
                     c("macrophage", "Mφ"),
                     c("mast", "Mast"),
                     c("mDC", "mDC"),
                     c("pDC", "pDC"),
                     c("monocyte", "Mono"),
                     c("neutrophil", "Neut"),
                     c("tcell_cd4", "Tc4"),
                     c("tcell_cd8", "Tc8"),
                     c('B.1', 'B.1'),
                     c('B.2', 'B.2'),
                     c('B.3', 'B.3'),
                     c('B.4', 'B.4')))
key_vector <- key_df[,2]
names(key_vector) <- key_df[,1]

## make a color coded list
colors <- c(rep('#8da0cb', 2), rep('#fc8d62', 6), rep('#66c2a5', 2), rep('#8da0cb', 4))
names(colors) <- key_df[,2]

## apply the key to the sle dataset
sle$ct1_abr <- sapply(sle$ct1, function(c) {key_vector[c]})
sle$ct2_abr <- sapply(sle$ct2, function(c) {key_vector[c]})

## sle
sle.fil.g <- graph_from_data_frame(sle[which(sle$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

sle.fil.g <- set_vertex_attr(sle.fil.g, "color", value = colors[get.vertex.attribute(sle.fil.g, "name")])
Warning: `get.vertex.attribute()` was deprecated in igraph 2.0.0.
ℹ Please use `vertex_attr()` instead.
This warning is displayed once every 8 hours.
Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.
## remove self-interacting nodes
g <- sle.fil.g
sle.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(sle.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_sle.svg',
    onefile=T)
plot(sle.fil.g_noself,
     vertex.label = V(sle.fil.g)$name,
     vertex.color = V(sle.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(sle.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topleft",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()
png 
  2 
### plot as heat-map type thing
ggplot(subset(sle, p.adj < 0.01),
       aes(x = ct1_abr,
           y = ct2_abr,
           size = log2.o.e,
           color = log10(p.adj))) +
  geom_point() +
  scale_color_viridis_b() +
  theme(axis.text.x = element_text(angle = 45, vjust = 1, hjust = 1))

## control
## apply the key to the sle dataset
ctrl$ct1_abr <- sapply(ctrl$ct1, function(c) {key_vector[c]})
ctrl$ct2_abr <- sapply(ctrl$ct2, function(c) {key_vector[c]})

ctrl.fil.g <- graph_from_data_frame(ctrl[which(ctrl$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

ctrl.fil.g <- set_vertex_attr(ctrl.fil.g, "color", value = colors[get.vertex.attribute(ctrl.fil.g, "name")])

## remove self-interacting nodes
g <- ctrl.fil.g
ctrl.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(ctrl.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_ctrl.svg',
    onefile=T)
plot(ctrl.fil.g_noself,
     vertex.label = V(ctrl.fil.g)$name,
     vertex.color = V(ctrl.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(ctrl.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("bottomright",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()
png 
  2 

Hypergeometric dist subclusts

Repeating the analysis above but including B-cell subclusters

# update annot dataframe to combine B-cell subclusters in a new column, "clust_bcellsubcl"
annot$clust_bcellsubcl <- annot$clust
bcellrows <- which(annot$clust %in% c('B-cell', 'plasmablast'))
row.names(bcell_seurat@meta.data) <- bcell_seurat@meta.data$cell_ID
annot[bcellrows,'clust_bcellsubcl'] <- as.character(bcell_seurat@meta.data[annot$cell_ID[bcellrows],
                                                                               'bcell_subclust'])

annot_norbcs <- annot[which(!(is.na(annot$clust_bcellsubcl))),]


# Combine T cell subsets in the clust_bcellsubcl
tcells <- subset(annot, ((basictype == 'tcell_cd4') | (basictype == 'tcell_cd8')))$cell_ID
annot[tcells,]$clust_bcellsubcl <- annot[tcells,'basictype']

# get an adjacency matrix for all subcluster cells
adj_matrices_subclust <- lapply(dists, function(d) { 
  tmp <- annot_norbcs[which(annot_norbcs$cell_ID %in% colnames(as.matrix(d))), c('cell_ID', 'clust_bcellsubcl')]
  annot_list <- tmp$clust_bcellsubcl
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1))
  }); names(adj_matrices_subclust) <- names(dists)


# get parameters for hypergeometric distribution
adj_matrix_hyperparams_subclust <- lapply(seq(1, length(adj_matrices_subclust)), function(n) {
  print(n)
  ## define the number of cell types within each distance matrix using the annot dataframe
  ### get the cells from the annotation dataframe
  nctypes <- table(annot_norbcs[which(annot_norbcs$cell_ID %in% colnames(as.matrix(dists[[n]]))), 'clust_bcellsubcl'])
  ### reorder the nctypes to be the same as the columns in the dataset
  nctypes <- nctypes[colnames(adj_matrices_subclust[[n]])]
  out <- adj_mat_to_hypergeo_params(adj_matrices_subclust[[n]],
                       nctypes)
  out$tissue <- names(dists)[n]
  return(out)
}) %>% bind_rows()
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# look at subclusters in control vs lupus samples
adj_matrix_hyperparams_subclust$disease <- 'control'
adj_matrix_hyperparams_subclust[which(adj_matrix_hyperparams_subclust$tissue %in% sle_samples),
                       'disease'] <- 'sle'

sle.v.control_subclust <- adj_matrix_hyperparams_subclust %>% 
  dplyr::group_by(ct1, ct2, disease) %>%
  summarise(m = sum(m),
            n = sum(n),
            k = sum(k),
            x = sum(x),
            expected.edges = max(c(qhyper(p=0.5,
                                          m = sum(m),
                                          k = sum(k),
                                          n = sum(n)),
                                   0.5)),
            p.val = max(c(phyper(q=sum(x),
                                 m=sum(m),
                                 k=sum(k),
                                 n=sum(n),
                                 lower.tail = F,
                                 log.p = F),
                          1e-30)))
`summarise()` has grouped output by 'ct1', 'ct2'. You can override using the `.groups` argument.
# add log2FC of observed over expected
sle.v.control_subclust$log2.o.e <- log2(sle.v.control_subclust$x/sle.v.control_subclust$expected.edges)
# add simple ratio
sle.v.control_subclust$o.e <- sle.v.control_subclust$x/sle.v.control_subclust$expected.edges

## adjust p-value for sle and controls separately
### sle
sle <- sle.v.control_subclust[which(sle.v.control_subclust$disease == 'sle'),]
sle$p.adj <- p.adjust(sle$p.val,
                      method = 'BH')
sle[which(sle$p.adj == 0),'p.adj'] <- 1e-30

### control
ctrl <- sle.v.control_subclust[which(sle.v.control_subclust$disease == 'control'),]            
ctrl$p.adj <- p.adjust(ctrl$p.val,
                      method = 'BH')



# plot the results
## apply the key to the sle dataset
sle$ct1_abr <- sapply(sle$ct1, function(c) {key_vector[c]})
sle$ct2_abr <- sapply(sle$ct2, function(c) {key_vector[c]})

## sle
sle.fil.g <- graph_from_data_frame(sle[which(sle$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

sle.fil.g <- set_vertex_attr(sle.fil.g, "color", value = colors[get.vertex.attribute(sle.fil.g, "name")])

## remove self-interacting nodes
g <- sle.fil.g
sle.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(sle.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_sle.svg',
    onefile=T)
plot(sle.fil.g_noself,
     vertex.label = V(sle.fil.g)$name,
     vertex.color = V(sle.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(sle.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topleft",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()
png 
  2 
## control
## apply the key to the sle dataset
ctrl$ct1_abr <- sapply(ctrl$ct1, function(c) {key_vector[c]})
ctrl$ct2_abr <- sapply(ctrl$ct2, function(c) {key_vector[c]})

ctrl.fil.g <- graph_from_data_frame(ctrl[which(ctrl$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

ctrl.fil.g <- set_vertex_attr(ctrl.fil.g, "color", value = colors[get.vertex.attribute(ctrl.fil.g, "name")])

## remove self-interacting nodes
g <- ctrl.fil.g
ctrl.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(ctrl.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_ctrl.svg',
    onefile=T)
plot(ctrl.fil.g_noself,
     vertex.label = V(ctrl.fil.g)$name,
     vertex.color = V(ctrl.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(ctrl.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topright",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()
png 
  2 

Proportion of each interaction type that occur within hotspots vs other areas

# make adjacency matrix of all immune cells
adj_matrices_imms <- lapply(dists, function(d) { 
  tmp <- annot[which(annot$cell_ID %in% rownames(as.matrix(d))), c('cell_ID', 'clust_bcellsubcl')]
  annot_list <- tmp$clust
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1,
                      collapse_query = F)) }) %>%
  bind_rows() %>% 
  ## merge in information about location of the query cells
  merge(.,
        bcell_seurat@meta.data[,c('cell_ID',
                                  'disease',
                                  'context')],
        by.x = 'row.names',
        by.y = 'cell_ID')
  
  ## rename the cell_ID column
  colnames(adj_matrices_imms)[1] <- "cell_ID"
  
  ## replace NA with 0
  adj_matrices_imms <- replace(adj_matrices_imms, is.na(adj_matrices_imms), 0)

# filter for just B.3 cells in LN
# make a dataframe with the number of interactions for each group within each context
cell_types <- colnames(adj_matrices_imms)[2:13]
df <- adj_matrices_imms %>% subset(celltype == 'B.3' & 
                                     disease == 'LN') %>%
  group_by(context) %>%
  summarise(across(all_of(cell_types), sum, .names = "{.col}")) %>%
  t(.) %>% as.data.frame(); colnames(df) <- df[1,]; df <- df[-1,]

# melt the df such that it can be plotte in ggplot2
df$interacting_cell <- row.names(df)
df_plot <- melt(df, id.vars = 'interacting_cell')
df_plot$value <- as.numeric(df_plot$value)
df_plot_props <- df_plot %>% group_by(interacting_cell) %>% summarise(contex = variable,
                                                                      prop_contex = value / sum(value))
Warning: Returning more (or less) than 1 row per `summarise()` group was deprecated in dplyr 1.1.0.
ℹ Please use `reframe()` instead.
ℹ When switching from `summarise()` to `reframe()`, remember that `reframe()` always returns an ungrouped data frame and
  adjust accordingly.
Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.
`summarise()` has grouped output by 'interacting_cell'. You can override using the `.groups` argument.
df_plot_ns <- df_plot %>% group_by(interacting_cell) %>% summarise(totn = sum(value))


plt <- ggplot() + 
  geom_bar(data = df_plot_props,
           aes(x = interacting_cell, 
               y = prop_contex, 
               fill = contex),
           color = 'black',
           stat = 'identity') +
  geom_text(data = df_plot_ns,
            aes(x = interacting_cell,
                y = 1.05,
                angle = 45,
                label = totn),
            size = 3,
            hjust = 0) +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  scale_y_continuous(expand = expand_scale(mult = c(0, 0.12)),
                     breaks = seq(0,1,0.25)) +
  scale_x_discrete(expand = expand_scale(mult = c(0, 0.1))) +
  theme(axis.text.x = element_text(angle = 45, hjust = 1),
        axis.title.y = element_blank()) +
  xlab(label = 'B.3-interacting Cell') +
  labs(fill = "Context")
Warning: `expand_scale()` was deprecated in ggplot2 3.3.0.
ℹ Please use `expansion()` instead.
This warning is displayed once every 8 hours.
Call `lifecycle::last_lifecycle_warnings()` to see where this warning was generated.
  
  
ggsave(plt,
       file = 'figures/B3_interactioncontext_SLE.svg',
       width = 5,
       height = 3.5,
       device = svg)
---
title: "B cell Analyses for cLN CosMx Paper"
output: html_notebook
editor_options: 
  chunk_output_type: inline
chunk_output_type: inline
---


# Load packages and prep data
## Load packages
```{r Load packages}
source('9. load_pkgs_BcellAnalysis.R')
loadfonts('pdf')
theme_set(theme_classic())
my_theme <- theme(
  text = element_text(family = 'ArialMT'),
  axis.line = element_line(linewidth = 1),
  axis.ticks = element_line(linewidth = 0.5),
  axis.title = element_text(size = 10),
  axis.text = element_text(size = 8),
  legend.title = element_text(size = 8),
  legend.text = element_text(size = 8)
)
theme_update(
  text = element_text(family = 'ArialMT'),
  axis.line = element_line(linewidth = 1),
  axis.ticks = element_line(linewidth = 0.5),
  axis.title = element_text(size = 10),
  axis.text = element_text(size = 8),
  legend.title = element_text(size = 8),
  legend.text = element_text(size = 8))
  

```
## Define custom functions

### Spatial analysis functions
#### Create adjacency matrix
Function that creates an adjacency matrix by querying each cell for the cell types of each target cell within a certian distance X, then sums across each cell type.
```{r}

# Define function
make_adj_mat <- function(
  # output of dist function  
  dist_obj, 
  # named list of cell names and cell types
  annot_list,
  # distance
  distX,
  # collapse query cells? (i.e. columns)
  collapse_query = T) {  
  
  ## retrieve matrix object from dist object
  dmat <-as.matrix(dist_obj)
  
  ## iterate through each query cell
  tmpmat <- sapply(colnames(dmat), function(cellid) {
    
    ### obtain all target cells within distX distance
    cell <- dmat[,cellid]
    cell_fil <- cell[which((cell < distX) & (cell != 0))]
    ### get the cell type of each cell and count using the annot dataframe
    out <- t(as.matrix(table(annot_list[names(cell_fil)])))
    row.names(out) <- cellid
    return(out)
  })
  
  ## put all cells together
  tmpmat <- rbind.fill.matrix(tmpmat)
  row.names(tmpmat) <- colnames(dmat)
  ## add clust to each query cell
  tmpmat <- as.data.frame(tmpmat)
  tmpmat$celltype <- annot_list[row.names(tmpmat)]
  
  ## collapse all query cells into clust as well
  if(collapse_query){
  
  outmat <- tmpmat %>% group_by(celltype) %>%
  summarise(across(everything(), ~ sum(., na.rm=T)))
  rnames <- outmat$celltype # make rownames the cell type 
  outmat <- as.matrix(outmat[,which(colnames(outmat) !='celltype')]) # remove celltype column
  row.names(outmat) <- rnames
  outmat <- outmat[colnames(outmat),] # make rownames and colnames the same order
  } else {
  outmat <- tmpmat
  }
  
  ## return the final dataframe
  return(outmat)
  
  }

```

#### Get hypergeo parameters

Going to use a hypergeometric distribution of edges ab, where a = celltype 1 (ct1), b = celltype2 (ct2), and:
* x = observed number of times ab is seen in the data
* m = total number of possible edges that include ab
    * if a != b: m = (Na * Nb)
    * if a == b: m = choose(Na,2)
* n = total number of possible edges that DON'T include ab: [ (((Nt*Nt)-Nt)/2) - m ] (cells can't be their own edge; draw a dummy matrix to make sense of this formula)
* k = number of edges in the dataset

Note that it's ok to add these values together across cells from the same "group"

```{r}
# Define function
adj_mat_to_hypergeo_params <- function(
    # adjacency matrix
    outmat,   
    # named vector of number of cells of each type in the dataset. Names must match adjacency matrix column and row names               
    nctypes)
  { 

    # ensure that all cell types are found in each of
    ## rownames outmat
    ## colnames outmat
    ## names of nctype
    if(any(row.names(outmat) != colnames(outmat))) {
      stop("Row names and column names of outmat do not match.")
    }
      
    if(!(all(row.names(outmat) %in% names(nctypes)) & all(names(nctypes) %in% row.names(outmat)))) {
      stop("Row names of outmat and names of nctype do not match.")
    }
    
  
    ## create output dataframe:
    ### determine unique combinations of cell types
    #### sort nctypes first to make sure that the combinations are made correctly
    out <- as.data.frame(combinations(n = length(names(nctypes)),
                                        r = 2,
                                        v = sort(names(nctypes)),
                                        repeats.allowed = T))
    colnames(out) <- c('ct1', 'ct2')
  
    ## calc total number of each cell type in dataset
    nt_cell <- sum(nctypes)
    nt_edge <- sum(outmat)/2
    
    ## for each cell in the adjacency matrix, define parameters of hypergeometric distribution
    ## if output = 'hyper_fit', then determine p values and expected number of edges given the params
    
    params <- t(apply(out, 1, function(r) {
        
        ### define ct1 and ct2
        ct1 = unlist(r['ct1'])
        ct2 = unlist(r['ct2'])
      
        ### define parameters of hypergeometric distribution
        x <- outmat[ct2, ct1]
        if(ct1==ct2) {
              m <- choose(nctypes[ct1], 2)} else {
              m <- nctypes[ct1] * nctypes[ct2]}
        n <- ((nt_cell * nt_cell) - nt_cell)/2 - m
        k <- nt_edge
        
        ### return parameters
        return(c(m, n, k, x))
          
        }))
    
    out <- cbind(out, params)
    colnames(out) <- c('ct1', 'ct2', 'm', 'n', 'k', 'x')   
    return(out)  
    }
    
```

#### Fit hypergeo parameters
This function fits the data to a hypergeometric distribution and calculates fold increased interactions over expected

```{r}
# Define function
fit_hyper_geo <- function(
    # the number of observed interactions between two cell ty pes
    observed_edge_n,   
    # the expected hyperparameters for those two cell types
    expec_hyperparams
    ){ 
  
  
  ## calc the expected number of edges
  expec <-  n*K/N
  
  ## calc the fold increase of observed / expected
  foldincr <- observed_edge_n / expec
  
  ## calc the p value 
  pval <- phyper(q=x,
                 m=m,
                 k=k,
                 n=n,
                 lower.tail = T,
                 log.p = T)
          
  ## return the data
  out = list(expec, foldincr, pval)
  names(out) = c('null.expec.edges', 'fold.incr.over.null', 'p.val')
  return(out)
}
  
```



```{r}
genemods_mle_findmarkers <- function(seurat_obj, # Seurat object
                                     rawdata = NULL, # sparse counts matrix, rows = genes, columns = cells
                                     mle_negm, # vector of mean negprobe counts per cell, see "insitutype" function
                                     mle_cohort, # dataframe of parameters used for fastCohorting, see "insitutype" function
                                     mle_nclust = NULL, # vector of length 2 specifying the minimum and maximum number of clusters for MLE cell to generate
                                     logfc_min = 0.5 # minimum log2fc required for genes to be designated as marker genes of a subcluster
                                     ) {
  
  
  # define raw data if undefined
  if(is.null(rawdata)) {
    rawdata <- seurat_obj@assays$nanostrRNA@counts
  }
  
  
  # define nclust if undefined
  if(is.null(mle_nclust)) {
    mle_nclust <- c(2, 
  ## the maximum number of clusters should either be the lesser of: (a) the number of genes or (b) the number of cells / 10, assuming that clusters on average should have at least 10 cells
                    min(c(nrow(raw), round(ncol(raw)/10))))
  }
  
  
  # Perform unsupervised cell clustering
    ## Cohort cells
    mle_coho <- fastCohorting(mat = mle_cohort,
                              gaussian_transform = TRUE)
    
    
    ## Cluster cells
    mle_unsup <- insitutype(counts = t(as.matrix(rawdata)),
                            neg = mle_ngem,
                            cohort = mle_coho,
                            n_clusts = mle_nclust,
                            reference_profiles = NULL) # NULL value runs unsupervised clustering
    
    
    ## Plot clusters
    mle_hm <- heatmap(sweep(mle_unsup$profiles,
                            1,
                            pmax(apply(mle_unsup$profiles, 1, max),
                                 .2),
                            "/"),
                      scale = "none",
                      main = "Subcluster Mean Expression Profiles")
    
    
    ## Add cluster data to Seurat object
    seurat_obj <- AddMetaData(seurat_obj, 
                              data.frame(mle_unsup$clust))
  
  
  # Run Marker Gene analysis
  Idents(object = seurat_obj) <- seurat_obj@meta.data$'mle_subclust' 

  mle_subclust_markers <- FindAllMarkers(seurat_obj,
                                         only.pos = TRUE,
                                         min.pct = 0.25)
  

  # Output
  out <- list()
  out$cell_cluster_heatmap <- mle_hm
  
  return(out)
  
}

 
```


## Load data
```{r Load data}
set.seed(0)
load("processed_data/cleaneddata.RData") # scRNAseq data
load("processed_data/cannot with distances from gloms.RData") # glomerular distance information from Patrick
context <- readRDS('processed_data/context4.RDS')
names(context) <- colnames(raw)
contam <- readRDS('processed_data/toomuchcontam.RDS') # gene contamination calls by Patrick

```

# Pre-process data

To remove genes that are "expressed" in cells due to poor segmentation, I will use Patrick's contamination dataset: "contaminating transcripts from imperfect cell segmentation – e.g. if a B-cell is surrounded by PCT cells, then when we occasionally draw a cell boundary wrong we’ll place some PCT transcripts in a B-cell. So if any of your clusters are driven by genes typical of another cell type, suspect an artifact. 
For each cell type x gene, the attached matrix measures how much the gene comes from the appropriate cell type vs. from contamination – higher values mean more pure / less contaminated data. You can use this to check if any of your B-cell cluster marker genes are contaminants. For differential expression, I’m only considering genes with values above 0.2."

Will use cotamstat.RDS to look at the contamination rates from the gene. We can look at each statistically significant gene 

## Define cell types and filter genes
Distribution of gene contamination scores
```{r Define Cell Types}

cd4_tcell_types <- c( "T CD4 memory",
                      "T CD4 naive",
                      "Treg")

cd8_tcell_types <- c( "T CD8 memory",
                      "T CD8 naive")

glomcell_types <- c("Podocyte",
                    "Glomerular.endothelium",
                    "Mesangial.cell",
                    "Parietal.epithelium")

vesslcell_types <- c("Vascular.pericyte",
                     "Peritubular.capillary.endothelium.1",
                     "Peritubular.capillary.endothelium.2",
                     "Ascending.vasa.recta.endothelium",
                     "Descending.vasa.recta.endothelium")

tubcell_types <- c("Connecting.tubule",
                   "PCT",
                   "Principal.cell",
                   "Type.A.intercalated.cell",
                   "Type.B.intercalated.cell",
                   "Pelvic.epithelium",
                   "Thick.ascending.limb.of.Loop.of.Henle",
                   "Indistinct.intercalated.cell",
                   "Transitional.urothelium",
                   "Epithelial.progenitor.cell")

innate_lymph <- c("NK")

interstcell_types <- c("Myofibroblast",
                       "Fibroblast")

# Define cell types
all_cell_types <- levels(as.factor(clust))

imm_cell_types <- c("B-cell",
                    "macrophage",
                    "mast",
                    "mDC",
                    "monocyte",
                    "neutrophil",
                    "NK",
                    "pDC",
                    "plasmablast",
                    "T CD4 memory",
                    "T CD4 naive",
                    "T CD8 memory",
                    "T CD8 naive",
                    "Treg")

b_cell_types <- c("B-cell",
                  "plasmablast")

my_cell_types <- c("macrophage",
                        "mast",
                        "mDC",
                        "monocyte",
                        "neutrophil",
                        "pDC")

str_cell_types <- subset(all_cell_types,
                           !(all_cell_types %in% imm_cell_types) &
                             (all_cell_types != "NotDet"))
                    

basic_cats <- function(x) {
  if(x %in% b_cell_types) { return('bcell') } else {
    if(x %in% cd4_tcell_types) { return('tcell_cd4') } else {
    if(x %in% cd8_tcell_types) { return('tcell_cd8') } else {
      if(x %in% my_cell_types) { return('mycell') } else {
        if(x %in% glomcell_types) {return('glomcell') } else {
          if(x %in% vesslcell_types) {return('vesslcell')} else {
            if(x %in% tubcell_types) {return('tubcell')} else {
              if(x %in% interstcell_types) {return('interstcell')} else {
                if(x %in% innate_lymph) {return('NKcell')}
                return("ERROR")
              }
            }
          }
        }
      }
    }
  }
  }
}

# organize metadata
annot <- merge(annot, data.frame(clust), by.x = "cell_ID", by.y = "row.names") 
# add cell calls
row.names(annot) <- annot$cell_ID
# annotate cells with larger cell type bins
annot$basictype <- sapply(annot$clust, basic_cats)
annot$alpha <- sapply(annot$basictype, function(x) {
  if(x %in% c('tcell', 'bcell', 'mycell')) {return(1)} else
    {return(0.2)}
})
# refine annotation of cd4 and cd8 t cells, to combine cells together
subset_tmp <- which(annot$basictype %in% c('tcell_cd4', 'tcell_cd8'))
annot[subset_tmp,'clust'] <- annot[subset_tmp,'basictype']


tmp <- as.data.frame(contam[,c(b_cell_types)])
tmp$maxval <- unlist(apply(tmp, 1, max))

ggplot(tmp, aes(x = maxval)) + geom_density()

```

```{r Filter genes}

# Define contaminated genes for B cells
b_cell_uncontam <- row.names(
  data.frame(!(contam[,b_cell_types])) %>% 
    filter_all(all_vars(.))
)


```



## Compute PCA and generate UMAP
Will use Seurat to obtain UMAP to cluster cells

```{r}
# Creat Seurat Object
## prepare all annotations
annot$context <- context[annot$cell_ID]
annot <- bind_cols(annot, cannot[annot$cell_ID,c('in.glom', 'inside.glom','position.vs.glom', 'closest.glom')])
## B-cells
bcell_seurat <- CreateSeuratObject(
  counts = raw[c(b_cell_uncontam, 'HBB'),],
  project = "LN_spatial",
  assay = "nanostrRNA",
  meta.data = annot
)

### only B-cell annotation
bcell_seurat <- subset(bcell_seurat,
                       subset = clust %in% b_cell_types)

# Scale data
bcell_seurat@meta.data$log10totalcounts <- sapply(bcell_seurat@meta.data$nCount_nanostrRNA, log10)
bcell_seurat <- ScaleData(bcell_seurat, 
                          features = c(b_cell_uncontam, 'HBB'),
                          model.use = 'negbinom',
                          vars.to.regress = 'log10totalcounts')

## negative values in the Scale Data column correspond to 0 values in the expression data. Rather than let pseudocounts cause "negative gene expression", these values should be corrected to be zero
tru_val <- as.vector(bcell_seurat@assays$nanostrRNA@counts)
scaled <- as.vector(bcell_seurat@assays$nanostrRNA@scale.data)
toplot <- data.frame(counts = tru_val,
                     scaled = scaled)

ggplot(toplot, aes(x = counts, y = scaled)) + geom_point(alpha = 0.2, size = 0.2)

# Make all scaled values < 0 equal 0 
bcell_seurat@assays$nanostrRNA@scale.data[which(bcell_seurat@assays$nanostrRNA@scale.data < 0)] <- 0

# Filter HBB+ cells
## Dist
cells_in_data <- colnames(bcell_seurat)

tmp <- data.frame(cell_ID = cells_in_data,
                  HBB = bcell_seurat@assays$nanostrRNA@scale.data['HBB', cells_in_data],
                  HBA = bcell_seurat@assays$nanostrRNA@scale.data['HBA1', cells_in_data])

ggplot(tmp, aes(x = HBA, y = HBB)) + geom_point()

HB_cells <- tmp[which((tmp$HBA > 2.5) |
                        tmp$HBB > 2.5), 'cell_ID']
nonHB_cells <- tmp$cell_ID[which(!(tmp$cell_ID %in% HB_cells))]

### update annot to include rbcs
annot[which(annot$cell_ID %in% HB_cells),'basictype'] <- 'rbc'
annot[which(annot$cell_ID %in% HB_cells),'clust'] <- 'rbc'

### No HB cells
bcell_seurat <- subset(bcell_seurat,
                       subset = cell_ID %in% nonHB_cells)

### No hemoglobin gene expression
all_genes <- row.names(bcell_seurat)
bcell_seurat <- subset(bcell_seurat,
                       features = all_genes[which(!(all_genes %in% c('HBB', 'HBA1')))])
bcell_all.genes <- rownames(bcell_seurat)

# Run PCA
## B-cells
bcell_seurat <- RunPCA(bcell_seurat, features = bcell_all.genes, npcs=20)
ElbowPlot(bcell_seurat, ndims=20)
bcell_seurat <- RunUMAP(bcell_seurat, dims = 1:20)

# Run UMAP
## B-cells
bcell_seurat <- FindNeighbors(bcell_seurat, dims = 1:20)
bcell_seurat <- FindClusters(bcell_seurat, resolution = 1)
bcell_seurat <- AddMetaData(bcell_seurat,
                  data.frame(bcell_seurat@reductions$umap@cell.embeddings))

DimPlot(bcell_seurat, reduction = 'umap') + plot_annotation(title='B-cell PCA Clusters')
ggplot(bcell_seurat@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=log10totalcounts)) +
  geom_point(size=0.5) +
  ggtitle('B-cell UMAP with RNA Counts')
  

```

# Subcluster cells with MLE
## Use MLEcell

```{r Subcluster cells, message=FALSE}
# b cell subclustering
bcell_cols <- which(clust %in% b_cell_types)
bcell_cnts <- raw[b_cell_uncontam,bcell_cols]
bcell_negm <- annot[bcell_cols,'negmean']
bcell_coho <- fastCohorting(annot[bcell_cols, c('Area',
                                                'AspectRatio',
                                                'Mean.PanCK', 
                                                'Mean.CD45',
                                                'Mean.DAPI')],
                        gaussian_transform = TRUE) 

bcell_unsup <- insitutype(counts = t(as.matrix(bcell_cnts)),
                          neg = bcell_negm,
                          cohort = bcell_coho,
                          bg = NULL, 
                    n_clusts = c(2, 4),
                    reference_profiles = NULL, # NULL value runs unsupervised clustering
                    ) 
```

## MLE heatmap

```{r Heatmaps of Original Clustering}
# B-cell heatmap
str(bcell_unsup)
round(head(bcell_unsup$prob),2)

bcell_hm <- heatmap(sweep(bcell_unsup$profiles,
                          1,
                          pmax(apply(bcell_unsup$profiles, 1, max),
                               .2),
                          "/"),
                    scale = "none",
                    main = "B-cell Subcluster Mean Expression Profiles")

```
## Flightpath plot

```{r Flightpath Plots}
## B-cells
# define cluster colors:
cols <- c('#a6cee3','#1f78b4','#b2df8a','#33a02c')
cols <- cols[seq_along(unique(bcell_unsup$clust))]
names(cols) <- unique(bcell_unsup$clust)

# make the flightpath plot
fp <- flightpath_plot(flightpath_result = NULL, insitutype_result = bcell_unsup, col = cols[bcell_unsup$clust])
class(fp)
print(fp)
ggsave(fp, file="figures/bcell_MLEcell_fp.png")

```


## Compare MLEcell and UMAP

```{r MLEcell Subclusters on UMAP}
# B-cells
bcell_seurat <- AddMetaData(bcell_seurat, 
                            data.frame(bcell_unsup$clust))

# rename subcluster identity
new = c('B.4','B.1','B.3','B.2')
new = factor(new, levels = c('B.1', 'B.2', 'B.3', 'B.4'))
key = data.frame(old = letters[1:4],
                 new = new)

bcell_seurat@meta.data$bcell_subclust <- sapply(bcell_seurat@meta.data$bcell_unsup.clust,
                                                function(o) {
                                                  return(key[which(key$old == o),'new'])
                                                })

bcell_seurat@meta.data$bcell_subclust <- factor(bcell_seurat@meta.data$bcell_subclust)

bcellcols <- c('#66c2a5','#fc8d62','#8da0cb','#e78ac3')

ggplot(bcell_seurat@meta.data,
       aes(x=UMAP_1,y=UMAP_2,color=bcell_subclust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols)

ggsave('figures/bcell_MLEcell_subclusts_UMAPspace.png',
       height=5.5)

saveRDS(bcell_seurat, 
        file = 'processed_data/bcell_seurat.RDS')
```

## Pub UMAP plot 

### Determine reasonable count filter

```{r}
lapply(seq(from = 1.5, to = 2.5, by =0.1), function(x) {
  print(x)
  
  # filter and rescale the data
  temp_seurat <- ScaleData(subset(bcell_seurat, subset = log10totalcounts > x), 
                          features = c(bcell_all.genes),
                          model.use = 'negbinom',
                          vars.to.regress = 'log10totalcounts')
  # Run PCA
  temp_seurat <- RunPCA(temp_seurat, features = bcell_all.genes, npcs=20)
  # Run UMAP
  temp_seurat <- RunUMAP(temp_seurat, dims = 1:20)
  # Plot
  Idents(object = temp_seurat) <- temp_seurat@meta.data$'bcell_unsup.clust' 
  DimPlot(temp_seurat,
          reduction = 'umap',
          ) + plot_annotation(title=paste0('B-cell Subclusters, log RNA count >', x))
})

```

cells with > 80 RNA counts seem to do best

### Plot UMAP

```{r}
#filter by ncounts
bcell_seurat_fil <- subset(bcell_seurat, subset = log10totalcounts > 1.9)

#run UMAP
bcell_seurat_fil <- RunPCA(bcell_seurat_fil, features = bcell_all.genes, npcs=20)
bcell_seurat_fil <- RunUMAP(bcell_seurat_fil, dims = 1:20)
Idents(object = bcell_seurat_fil) <- bcell_seurat_fil@meta.data$'bcell_subclust' 

# remove old UMAP cols from metadata
bcell_seurat_fil@meta.data <- bcell_seurat_fil@meta.data[,which(!(colnames(bcell_seurat_fil@meta.data) %in% c('UMAP_1', 'UMAP_2')))]

# Add new UMAP cols
bcell_seurat_fil <- AddMetaData(bcell_seurat_fil,
                  data.frame(bcell_seurat_fil@reductions$umap@cell.embeddings))


# Make sure it's not too batchy
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=tissuename)) +
  geom_point(size=1) +
  facet_wrap(~tissuename) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())

# Plot
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=bcell_subclust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())

ggsave(file = 'figures/bcellsubclust_UMAP.svg',
       width = 4,
       height = 3,
       device = svg)


# Plot plasmablast and B-cell identity
ggplot(bcell_seurat_fil@meta.data,
       aes(x=UMAP_1, 
           y=UMAP_2,
           color=clust)) +
  geom_point(size=1) +
  scale_color_manual(values = bcellcols,
                    guide = guide_legend(title = "Patrick\ncell types",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  theme(axis.title.y = element_blank(),
        axis.title.x = element_blank())

ggsave(file = 'figures/bcellPlasma_UMAP.svg',
       width = 4,
       height = 3,
       device = svg)


```

# Subcluster vs other variables

## Continuous variables

```{r Assess Continuous Variables, message=FALSE}
## define continuous variables
contvars <- list("totalcounts", "Area", "Mean.PanCK", "Max.PanCK", "Mean.CD45", "Max.CD45", "Mean.DAPI", "Max.DAPI")


## B-cells
# MLE-cell vs continuous variables
plts <- lapply(contvars, function(d) {
  ggplot(bcell_seurat@meta.data,
         aes_string(x = "bcell_subclust",
                    y = d)) + geom_violin() +
    geom_jitter(size = 0.5, alpha = 0.1) +
    scale_y_continuous(trans='log10')
  
})

plts <- ggarrange(plotlist=plts, labels = contvars, common.legend = F)
ggsave(filename = 'figures/bcell_MLEcellsubclusts_contvar_metadats.png',
       plts,
       width = 20,
       height = 14)
```


## Discrete variables

```{r Assess Discrete Variables, message=FALSE}
## Define discrete variables
discvars <- list("tissuename", "class", "clust", 'context', 'position.vs.glom')

## B-cells
plts <- lapply(discvars, function(d) {
  ggplot(bcell_seurat@meta.data,
         aes_string(x = "bcell_subclust", fill = d)) +
    geom_bar()
  
})

plts <- ggarrange(plotlist=plts,
                  labels = discvars, 
                  common.legend = F)

ggsave(filename = 'figures/bcell_MLEcell_discvar_metadats.png',
       plts,
       width = 20,
       height = 15)
```


## Lupus class

```{r Look at Lupus Class, message=FALSE}
# B-cells
## look at over-representation of clusters in each class
bcell_unsup_lupusclass_chisq <- chisq.test(table(bcell_seurat@meta.data$class,
                                                 bcell_seurat@meta.data$bcell_subclust))
bcell_unsup_lupusclass_chisq_res <- melt(bcell_unsup_lupusclass_chisq$residuals)
colnames(bcell_unsup_lupusclass_chisq_res) <- c('class',
                                                'cluster',
                                                'residual')

bcell_unsup_lupusclass_chisq_res %>% 
  arrange(plyr::desc(residual))

## most over-represented cell subset in each cluster, along with residual
bcell_unsup_class_overrep <- bcell_unsup_lupusclass_chisq_res %>%
  group_by(cluster) %>%
  slice_max(n=1, order_by=residual) %>%
  summarize(cluster=cluster, class=class, max_residual=residual, )

## plot class vs cluster with underlying plot of the class most over-represented and its chi-sq residual
## Most interesting are c, e, h, m, and t (residuals > 5)
ggplot() +
  geom_bar(data=bcell_seurat@meta.data,
           color="black",
           aes(x=bcell_subclust,
               fill=class)) +
  geom_point(data=bcell_unsup_class_overrep,
             color="black",
             shape=21,
             aes(x=cluster,
                 y=-30,
                 fill=class,
                 size=max_residual)) +
  labs(title = 'B-cell Subcluster Prevalence across Lupus Nephritis Classes') +
  ylab('Number of cells') +
  xlab('B-cell subluster ID') +
  guides(fill=guide_legend(title="LN Class"),
         size=guide_legend(title='ChiSq Residual'))

ggsave('figures/bcell_subclusterIDvsLNClass.png')


# ok, screw that. Let's do a diseased vs undiseased test first instead
bcell_seurat@meta.data$disease = 'LN'
bcell_seurat@meta.data[which(bcell_seurat@meta.data$class == 'control'),'disease'] <- 'Control'

bcell_subclust_chisq_dz <- bind_rows(lapply(new, function(cl) {
  print(cl)
  df <- bcell_seurat@meta.data
  df$cl <- cl
  df$cl <- as.character(df$cl)
  df[which(df$bcell_subclust != cl),'cl'] <- 'other clusters'
  chisq <- chisq.test(table(df$disease, df$cl))
  return(cbind(data.frame(subcluster = cl), broom::tidy(chisq)))
  
  
}))

bcell_subclust_chisq_dz$p.value.adj = p.adjust(bcell_subclust_chisq_dz$p.value,
                                               method = 'BH')

fig <- ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(y = disease,
               fill = bcell_subclust),
           position = 'fill',
           color = 'black') +
  geom_point(data = data.frame(x=c(0.15, 0.69),
                               y=c('control','sle')),
             aes(x=x,y=y),
             shape=8) +
  scale_fill_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  scale_x_continuous(labels = scales::percent) +
  ylab(label = element_blank()) +
  xlab(label = element_blank())


ggsave(filename = 'figures/bcell_subclust_lupusclass.svg',
       plot = fig,
       width = 3,
       height = 1,
       units = "in",
       device = svg)

bcell_subclust_chisq_dz

```


## Tubulointerstitial hotspots
```{r}
context <- readRDS('processed_data/context4.RDS')
context <- annot[,c('cell_ID', 'context')]
#bcell_seurat@meta.data <- merge(bcell_seurat@meta.data, context, by = 'cell_ID')

df <- melt(table(bcell_seurat@meta.data[,#which(bcell_seurat@meta.data$disease == 'LN'),
                             c('context', 'bcell_subclust', 'disease')]))

# Get the percentage of B.3 cells in hotspots, and overall
all_cell_perc <- df %>% group_by(bcell_subclust) %>% summarize(sum(value)/sum(df$value))
hotspot_perc <- subset(df, context == 'hotspot') %>% group_by(bcell_subclust) %>% summarize(sum(value) / sum(df[which(df$context == 'hotspot'),'value']))

# perform a chisq
chisqtable <- table(data.frame(
  B.3 = sapply(bcell_seurat@meta.data$bcell_subclust, function(c) {c=='B.3'}),
  hotspot = sapply(bcell_seurat@meta.data$context, function(c) {c=='hotspot'})))
chisq.test(chisqtable,
              )

fig <- ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(y = bcell_subclust,
               fill = context),
           position = 'fill',
           color = 'black') +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  scale_x_continuous(labels = scales::percent) +
  ylab(label = 'B-cell\nSubcluster') +
  xlab(label = element_blank()) +
  labs(fill = "Location") +
  theme(legend.position = "bottom",
        legend.key.size = unit(0.3, "cm"),
        legend.margin = margin(t = -0.5, unit = "cm"),
        legend.title = element_text(size = 10)) +
  guides(fill = guide_legend(title.position = 'top',
                             nrow = 4))

ggsave(filename = 'figures/bcell_subclust_hotspots.svg',
       plot = fig,
       width = 2,
       height = 2,
       units = "in",
       device = svg)

```


# Subcluster DEGs

## Identify marker genes

```{r Identify Subcluster Marker Genes, message=FALSE}

# B-cells
# set identity of cells for finding markers to the clusters discovered with MLEcell
Idents(object = bcell_seurat) <- bcell_seurat@meta.data$'bcell_subclust' 

bcell_MLE_markers <- FindAllMarkers(bcell_seurat,
                                    only.pos = TRUE,
                                    min.pct = 0.25,
                                    logfc.threshold = 0.25)

bcell_MLE_markers <-  merge(bcell_MLE_markers, 
                                data.frame(contam[,c("B-cell", "plasmablast")]), 
                            by.x = 'gene',
                            by.y = 'row.names',
                            all.x=T)

# Retrive top statistically significant markers
bcell_MLE_markers_top5 <- bcell_MLE_markers %>%
  filter(p_val_adj < 0.01) %>%
    group_by(cluster) %>%
    slice_max(n = 5, order_by = avg_log2FC)

# Plot the cluster and the top three markers on UMAP, with an additional label showing the top 5 genes with genes affected by contamination in RED
for(cl in unique(bcell_MLE_markers_top5$cluster)) {
  
  df <- bcell_MLE_markers_top5 %>%
    filter(cluster == cl) %>%
    arrange(desc(avg_log2FC))

  plts <-lapply(df$gene, function(x) {
    FeaturePlot(bcell_seurat_fil, x, max.cutoff="q99", pt.size=0.2) + ggtitle(x)
  })
  
  dat <- bcell_seurat_fil@meta.data
  dat$alp_cluster <- sapply(dat$bcell_subclust,
                            function(x){
                              if(x==cl){
                                return(1)} else {
                                  return(0.2)
                              }})
  col_ref_table <- data.frame(bcell_subclust = new,
                              clust_color = bcellcols[1:length(new)])
  col_ref_table$clust_color <- apply(col_ref_table,
                                     1,
                                     function(x){
                                        if(x[1]==cl) {
                                          return(x[2])
                                        } else {
                                          return('#9E9E9E')
                                        }
                                      })
                              
  
  p4 <- ggplot(dat,
               aes(x=UMAP_1,
                   y=UMAP_2,
                color=bcell_subclust,
                alpha=alp_cluster)) +
  geom_point(size=0.2) +
  scale_color_manual(values=col_ref_table$clust_color) +
  theme(legend.position="none",
        plot.margin= margin(0.5,6,0.5,0.5,unit='cm'))
  
  
  df$pval_adj <- sapply(df$p_val_adj, function(x) sprintf("%.2e", x))
  df$log2FC <- sapply(df$avg_log2FC, function(x) round(x, digits = 2))
    
  p5 <- gridExtra::tableGrob(df[,c('gene',
                                   'p_val_adj',
                                   'log2FC',
                                   'pct.1',
                                   'pct.2'
                                   )])
  
  
  if(length(plts)==1) {G1 <- (plts[[1]] | plot_spacer() | plot_spacer()) / (p4|p5|plot_spacer()) } else 
    if(length(plts)==2) {G1 <- (plts[[1]] | plts[[2]] | plot_spacer()) / (p4|p5|plot_spacer()) } else
      {G1 <- (plts[[1]] | plts[[2]] | plts[[3]]) / (p4|p5|plot_spacer()) }
  
  ggsave(paste0('figures/bcell_subclust_',cl,'_markergenes.png',
                                  sep=""),
         G1,
         width=10,
         height=5,
         units='in')
}

write.csv(bcell_MLE_markers, paste0('bcell_MLE_markers.csv'))

```


## DEGs of interest

```{r}
goi <- c('IGHM', 'IGHA1', 'IGHG1', 'XBP1', 'HLA-DQA1', 'HLA-DPA1')

# Make a list of feature plots
figs <- lapply(goi, function(g) {
  FeaturePlot(bcell_seurat_fil,
                   features = g,
              pt.size = 0.1,
              max.cutoff = 'q95') + 
    ## add my theme
    my_theme +
    ## make it publication ready
    theme(
      axis.text.x = element_blank(),
      axis.text.y = element_blank(),
      axis.title.x = element_blank(),
      axis.title.y = element_blank(),
      plot.title = element_text(face = "italic",
                                size = 10),
      axis.ticks = element_blank(),
      legend.position = "none"
)})

# Put feature plots together
faceted_plot <- wrap_plots(plotlist = figs,
                           ncol = 2)

# Plot it
ggsave(filename = 'figures/bcell_subclust_goi.svg',
       plot = faceted_plot,
       width = 2.5,
       height = 4,
       units = "in",
       device = svg)




```

# Lupus vs control analyses

## Number of cells

```{r}
df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease) %>%
  summarize(number_bcells = n())

wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_bcells']),
            unlist(df[which(df$disease == 'LN'), 'number_bcells']),
            alternative = 'less')


ggplot(df,
       aes(x = disease,
           y = number_bcells,
           fill = disease)) +
  geom_boxplot(outlier.shape = NA) +
  geom_jitter() +
  scale_fill_manual(values = c('#0571b0', '#ca0020')) +
  ylab('Number of B-cells') +
  xlab(label = element_blank()) +
  theme(legend.position='none')

ggsave(file = 'figures/lupuscontrols_numbcells.svg',
       width = 1.5,
       height = 1.5,
       device = svg)


```

## Number of each subcluster
```{r}
df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease, bcell_subclust) %>%
  summarize(number_cells = n())

lapply(unique(df$bcell_subclust), function(cl) {
  df <- df[which(df$bcell_subclust == cl),]
  wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_cells']),
            unlist(df[which(df$disease == 'LN'), 'number_cells']))
})

ggplot(df,
       aes(x = disease,
           y = number_cells,
           fill = disease)) +
  geom_boxplot(outlier.shape = NA) +
  geom_jitter(width = 0.15) +
  scale_fill_manual(values = c('#0571b0', '#ca0020')) +
  facet_wrap(~bcell_subclust) +
  ylab('Number of B-cells') +
  xlab(label = element_blank()) +
  theme(legend.position='none')

ggsave(file = 'figures/lupuscontrols_numbcells_subclust.svg',
       width = 3.5,
       height = 3.5,
       device = svg)


```


## Proportion of each subcluster

```{r}
bcell_seurat@meta.data <- bcell_seurat@meta.data[,which(
  !(duplicated(colnames(bcell_seurat@meta.data)))
)]

df <- bcell_seurat@meta.data %>%
  filter(!tissue %in% c("SP20_1098", "SP20_10838")) %>%
  group_by(tissue, disease, bcell_unsup.clust) %>%
  summarize(number_cells = n()) %>%
  mutate(freq = number_cells/sum(number_cells))


wilcox.test(unlist(df[which(df$disease == 'Control'), 'number_cells']),
            unlist(df[which(df$disease == 'LN'), 'number_cells']))

ggplot() +
  geom_bar(data = bcell_seurat@meta.data,
           aes(x = disease,
               fill = bcell_subclust),
           position = 'fill',
           color = 'black') +
  geom_point(data = data.frame(y=c(0.15, 0.70),
                               x=c('Control', 'LN')),
             aes(x=x,y=y),
             shape=8) +
  scale_fill_manual(values = bcellcols,
                    guide = guide_legend(title = "B-cell\nsubcluster",
                                         keyheight = 0.5,
                                         keywidth = 0.5)) +
  scale_y_continuous(labels = scales::percent) +
  ylab(label = element_blank()) +
  xlab(label = element_blank())
  

ggsave(file = 'figures/lupuscontrols_propsubclusts.svg',
       width = 2.5,
       height = 3,
       device = svg)

```

# Visual analyses


## Load data for visual analyses
 
```{r}
# load data
xycoords <- customlocs
row.names(xycoords) <- colnames(raw)

# calculate pairwise distance matrices for all immune cells
dists <- sapply(unique(annot$tissue), function(tis) { 
  
  cells = filter(annot, (tissue == tis &
                           !(cell_ID %in% HB_cells) & # remove hemoglobin+ cells from immune cells
                        basictype %in% c('tcell_cd4',
                                         'tcell_cd8',
                                         'bcell',
                                         'mycell'))) %>% dplyr::select(cell_ID) %>% unlist
  return(dist(xycoords[cells,]))
  
  })



```


## Number of cells within 50 cells

TO perform this analysis, each tissue must be assessed independently to prevent too muchy memory from being used.

```{r}
# define function that retrieves the 50 closest cells for a given set of "cells of interest"
find_closest_cells <- function(distance_matrix,
                               num_closest_cells,
                               cois = subset(annot, basictype == 'bcell')$cell_ID) { 
  
  ## filter for B cells only
  distance_matrix <- sapply(cois, 
                function(c) {
                  usedist::dist_get(distance_matrix,
                                    c,
                                    cells)
                            })
  row.names(distance_matrix) <- cells
                            
  print(dim(distance_matrix))
  cell_names <- row.names(distance_matrix)
  num_cells <- ncol(distance_matrix)
  closest_cells_list <- vector("list", num_cells)
  
  for (i in 1:num_cells) {
    distances <- distance_matrix[,i]
    closest_indices <- order(distances)[1:num_closest_cells]
    
    closest_cell_names <- cell_names[closest_indices]
    closest_cells_list[[i]] <- closest_cell_names
  }
  
  names(closest_cells_list) <- colnames(distance_matrix)
  return(closest_cells_list)
}

# define function that takes a list of cells and counts the number of immune cells
count_imm_cells <- function(cell_list) {
  
  annot_subset <- subset(annot, basictype %in% (c('bcell',
                                                  'mycell',
                                                  'tcell',
                                                  'NKcell')))
  return(sum(sapply(cell_list, function(c) {c %in% annot_subset$cell_ID})))
}

# iterate through each tissue sample to assess the number of immune cells next to each cell
## initialize empty list
tissue_ids <- unique(annot$tissue)
num_tissues <- length(tissue_ids)
tissue_bcell_nimmune_cells <- vector("list", num_tissues)

## iterate through each tissue's xycords:
for(i in 1:num_tissues) {
  print(paste0('Analzying tissue ', tissue_ids[i]))
  ### compute distance matrix
  cells = filter(annot, (tissue == tissue_ids[i]))$cell_ID
  distance_matrix <- dist(xycoords[cells,])
  
  ### get 50 closest cells to each B cell (not counting the cell itself..)
  closest_cells <- find_closest_cells(distance_matrix,
                                      51,
                                      subset(annot,
                                             (basictype == 'bcell' &
                                               tissue == tissue_ids[i]))$cell_ID)  
  rm(distance_matrix)
  gc() # save memory
  ### count number of immune cells in each list of 50
  imm_cell_nums <- lapply(closest_cells, count_imm_cells)
  ### populate the empty list
  tissue_bcell_nimmune_cells[[i]] <- data.frame(cell_ID = names(closest_cells),
                                                n_imm_cells = unlist(imm_cell_nums)-1) # remove one from each to remove self
} 

tissue_bcell_nimmune_cells_df <- bind_rows(tissue_bcell_nimmune_cells)

## plot data, separating controls and SLE patients
### Prep data
tissue_bcell_nimmune_cells_df$imm_hotspot <- as.numeric(tissue_bcell_nimmune_cells_df$n_imm_cells > 0)
tissue_bcell_nimmune_cells_df <- merge(tissue_bcell_nimmune_cells_df, bcell_seurat@meta.data[,c('bcell_subclust', 'disease')], by = 'row.names')


tab <- table(tissue_bcell_nimmune_cells_df[which(tissue_bcell_nimmune_cells_df$disease=='LN'),c('bcell_subclust', 'imm_hotspot')])
tab[,1] / tab[,2]



### column for whether a cell is in an tubulointerstitial hotspot
df <- tissue_bcell_nimmune_cells_df
df$context <- sapply(df$cell_ID, function(ci) {annot[ci,'context']})
df$tubinst_hotspot <- sapply(df$context, function(c) {c == 'hotspot'})


### save df
write.csv(df, file = "num_imm_wi_50.csv")

### read df
df <- read.csv("num_imm_wi_50.csv", row.names = 1)

### plot data
ggplot(df,
       aes(x = n_imm_cells,
           fill = as.factor(context))) +
  geom_histogram(color = 'black') +
  facet_wrap(disease~ bcell_subclust,
             scales = 'free_y',
             nrow = 2) +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  ylab(label = element_blank()) +
  xlab(label = 'Number of Nearby Immune Cells') +
  labs(fill = "Location") +
  theme(legend.position = "bottom",
        legend.key.size = unit(0.3, "cm"),
        legend.margin = margin(t = 0, unit = "cm"),
        legend.title = element_text(size = 10))

ggsave(file = 'figures/lupuscontrols_numbimmcells_location_subclust.svg',
       width = 6,
       height = 3.5,
       device = svg)

```



## Network Analysis
### Hypergeometric dists clust

```{r}
# fit hypergeometric parameters for each cell type for each sample
adj_matrices <- lapply(dists, function(d) { 
  tmp <- annot[which(annot$cell_ID %in% colnames(as.matrix(d))), c('cell_ID', 'clust')]
  annot_list <- tmp$clust
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1))
  }); names(adj_matrices) <- names(dists)


# get parameters for hypergeometric distribution
adj_matrix_hyperparams <- lapply(seq(1, length(adj_matrices)), function(n) {
  print(n)
  ## define the number of cell types within each distance matrix using the annot dataframe
  ### get the cells from the annotation dataframe
  nctypes <- table(annot[which(annot$cell_ID %in% colnames(as.matrix(dists[[n]]))), 'clust'])
  ### reorder the nctypes to be the same as the columns in the dataset
  nctypes <- nctypes[colnames(adj_matrices[[n]])]
  out <- adj_mat_to_hypergeo_params(adj_matrices[[n]],
                       nctypes)
  out$tissue <- names(dists)[n]
  return(out)
}) %>% bind_rows()

# look at the networks control vs lupus cases
## define control and sle samples
control_samples <- unique(annot[which(annot$class == 'control'),'tissue'])
sle_samples <- unique(annot[which(annot$class != 'control'), 'tissue'])
adj_matrix_hyperparams$disease <- 'control'
adj_matrix_hyperparams[which(adj_matrix_hyperparams$tissue %in% sle_samples),
                       'disease'] <- 'sle'

adj_matrix_hyperparams$ct1.2 <- t(apply(adj_matrix_hyperparams[,c('ct1', 'ct2')],
                                      1,
                                      function(r) {
                                        paste(unlist(r), 
                                              sep = '_')
                                      }))

## do the following to each set of samples:
### (1) sum hypergeometric distribution hyperparameters (m, n, k) and observed edges (x)
### (2) calculate the expected number of edges (expected.edges)
### (3) calculate the fold increase over expected (fold.incr)
### (4) calculate a p-value

sle.v.control.clust <- adj_matrix_hyperparams %>% 
  dplyr::group_by(ct1, ct2, disease) %>%
  summarise(m = sum(m),
            n = sum(n),
            k = sum(k),
            x = sum(x),
            expected.edges = max(c(qhyper(p=0.5,
                                          m = sum(m),
                                          k = sum(k),
                                          n = sum(n)),
                                   0.5)),
            p.val = max(c(phyper(q=sum(x),
                                 m=sum(m),
                                 k=sum(k),
                                 n=sum(n),
                                 lower.tail = F,
                                 log.p = F),
                          1e-30)))

# add log2FC of observed over expected
sle.v.control.clust$log2.o.e <- log2(sle.v.control.clust$x/sle.v.control.clust$expected.edges)

## adjust p-value for sle and controls separately
### sle
sle <- sle.v.control.clust[which(sle.v.control.clust$disease == 'sle'),]
sle$p.adj <- p.adjust(sle$p.val,
                      method = 'BH')
### control
ctrl <- sle.v.control.clust[which(sle.v.control.clust$disease == 'control'),]            
ctrl$p.adj <- p.adjust(ctrl$p.val,
                      method = 'BH')


# plot the results
## make a key of abbreviated names
key_df <- t(data.frame(c('B-cell', "Bc"),
                     c("plasmablast", "PC"),
                     c("macrophage", "Mφ"),
                     c("mast", "Mast"),
                     c("mDC", "mDC"),
                     c("pDC", "pDC"),
                     c("monocyte", "Mono"),
                     c("neutrophil", "Neut"),
                     c("tcell_cd4", "Tc4"),
                     c("tcell_cd8", "Tc8"),
                     c('B.1', 'B.1'),
                     c('B.2', 'B.2'),
                     c('B.3', 'B.3'),
                     c('B.4', 'B.4')))
key_vector <- key_df[,2]
names(key_vector) <- key_df[,1]

## make a color coded list
colors <- c(rep('#8da0cb', 2), rep('#fc8d62', 6), rep('#66c2a5', 2), rep('#8da0cb', 4))
names(colors) <- key_df[,2]

## apply the key to the sle dataset
sle$ct1_abr <- sapply(sle$ct1, function(c) {key_vector[c]})
sle$ct2_abr <- sapply(sle$ct2, function(c) {key_vector[c]})

## sle
sle.fil.g <- graph_from_data_frame(sle[which(sle$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

sle.fil.g <- set_vertex_attr(sle.fil.g, "color", value = colors[get.vertex.attribute(sle.fil.g, "name")])

## remove self-interacting nodes
g <- sle.fil.g
sle.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(sle.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_sle.svg',
    onefile=T)
plot(sle.fil.g_noself,
     vertex.label = V(sle.fil.g)$name,
     vertex.color = V(sle.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(sle.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topleft",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()


### plot as heat-map type thing
ggplot(subset(sle, p.adj < 0.01),
       aes(x = ct1_abr,
           y = ct2_abr,
           size = log2.o.e,
           color = log10(p.adj))) +
  geom_point() +
  scale_color_viridis_b() +
  theme(axis.text.x = element_text(angle = 45, vjust = 1, hjust = 1))

## control
## apply the key to the sle dataset
ctrl$ct1_abr <- sapply(ctrl$ct1, function(c) {key_vector[c]})
ctrl$ct2_abr <- sapply(ctrl$ct2, function(c) {key_vector[c]})

ctrl.fil.g <- graph_from_data_frame(ctrl[which(ctrl$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

ctrl.fil.g <- set_vertex_attr(ctrl.fil.g, "color", value = colors[get.vertex.attribute(ctrl.fil.g, "name")])

## remove self-interacting nodes
g <- ctrl.fil.g
ctrl.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(ctrl.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_ctrl.svg',
    onefile=T)
plot(ctrl.fil.g_noself,
     vertex.label = V(ctrl.fil.g)$name,
     vertex.color = V(ctrl.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(ctrl.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("bottomright",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()



```





### Hypergeometric dist subclusts

Repeating the analysis above but including B-cell subclusters

```{r}
# update annot dataframe to combine B-cell subclusters in a new column, "clust_bcellsubcl"
annot$clust_bcellsubcl <- annot$clust
bcellrows <- which(annot$clust %in% c('B-cell', 'plasmablast'))
row.names(bcell_seurat@meta.data) <- bcell_seurat@meta.data$cell_ID
annot[bcellrows,'clust_bcellsubcl'] <- as.character(bcell_seurat@meta.data[annot$cell_ID[bcellrows],
                                                                               'bcell_subclust'])

annot_norbcs <- annot[which(!(is.na(annot$clust_bcellsubcl))),]


# Combine T cell subsets in the clust_bcellsubcl
tcells <- subset(annot, ((basictype == 'tcell_cd4') | (basictype == 'tcell_cd8')))$cell_ID
annot[tcells,]$clust_bcellsubcl <- annot[tcells,'basictype']

# get an adjacency matrix for all subcluster cells
adj_matrices_subclust <- lapply(dists, function(d) { 
  tmp <- annot_norbcs[which(annot_norbcs$cell_ID %in% colnames(as.matrix(d))), c('cell_ID', 'clust_bcellsubcl')]
  annot_list <- tmp$clust_bcellsubcl
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1))
  }); names(adj_matrices_subclust) <- names(dists)


# get parameters for hypergeometric distribution
adj_matrix_hyperparams_subclust <- lapply(seq(1, length(adj_matrices_subclust)), function(n) {
  print(n)
  ## define the number of cell types within each distance matrix using the annot dataframe
  ### get the cells from the annotation dataframe
  nctypes <- table(annot_norbcs[which(annot_norbcs$cell_ID %in% colnames(as.matrix(dists[[n]]))), 'clust_bcellsubcl'])
  ### reorder the nctypes to be the same as the columns in the dataset
  nctypes <- nctypes[colnames(adj_matrices_subclust[[n]])]
  out <- adj_mat_to_hypergeo_params(adj_matrices_subclust[[n]],
                       nctypes)
  out$tissue <- names(dists)[n]
  return(out)
}) %>% bind_rows()

# look at subclusters in control vs lupus samples
adj_matrix_hyperparams_subclust$disease <- 'control'
adj_matrix_hyperparams_subclust[which(adj_matrix_hyperparams_subclust$tissue %in% sle_samples),
                       'disease'] <- 'sle'

sle.v.control_subclust <- adj_matrix_hyperparams_subclust %>% 
  dplyr::group_by(ct1, ct2, disease) %>%
  summarise(m = sum(m),
            n = sum(n),
            k = sum(k),
            x = sum(x),
            expected.edges = max(c(qhyper(p=0.5,
                                          m = sum(m),
                                          k = sum(k),
                                          n = sum(n)),
                                   0.5)),
            p.val = max(c(phyper(q=sum(x),
                                 m=sum(m),
                                 k=sum(k),
                                 n=sum(n),
                                 lower.tail = F,
                                 log.p = F),
                          1e-30)))


# add log2FC of observed over expected
sle.v.control_subclust$log2.o.e <- log2(sle.v.control_subclust$x/sle.v.control_subclust$expected.edges)
# add simple ratio
sle.v.control_subclust$o.e <- sle.v.control_subclust$x/sle.v.control_subclust$expected.edges

## adjust p-value for sle and controls separately
### sle
sle <- sle.v.control_subclust[which(sle.v.control_subclust$disease == 'sle'),]
sle$p.adj <- p.adjust(sle$p.val,
                      method = 'BH')
sle[which(sle$p.adj == 0),'p.adj'] <- 1e-30

### control
ctrl <- sle.v.control_subclust[which(sle.v.control_subclust$disease == 'control'),]            
ctrl$p.adj <- p.adjust(ctrl$p.val,
                      method = 'BH')



# plot the results
## apply the key to the sle dataset
sle$ct1_abr <- sapply(sle$ct1, function(c) {key_vector[c]})
sle$ct2_abr <- sapply(sle$ct2, function(c) {key_vector[c]})

## sle
sle.fil.g <- graph_from_data_frame(sle[which(sle$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

sle.fil.g <- set_vertex_attr(sle.fil.g, "color", value = colors[get.vertex.attribute(sle.fil.g, "name")])

## remove self-interacting nodes
g <- sle.fil.g
sle.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(sle.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_sle.svg',
    onefile=T)
plot(sle.fil.g_noself,
     vertex.label = V(sle.fil.g)$name,
     vertex.color = V(sle.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(sle.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topleft",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()


## control
## apply the key to the sle dataset
ctrl$ct1_abr <- sapply(ctrl$ct1, function(c) {key_vector[c]})
ctrl$ct2_abr <- sapply(ctrl$ct2, function(c) {key_vector[c]})

ctrl.fil.g <- graph_from_data_frame(ctrl[which(ctrl$p.adj < 0.01),
                                                      c('ct1_abr',
                                                        'ct2_abr',
                                                        'log2.o.e',
                                                        'p.adj'
                                                        )],
                                   directed = F)

ctrl.fil.g <- set_vertex_attr(ctrl.fil.g, "color", value = colors[get.vertex.attribute(ctrl.fil.g, "name")])

## remove self-interacting nodes
g <- ctrl.fil.g
ctrl.fil.g_noself <- igraph::simplify(g, remove.loops = TRUE)
custom_layout <- layout_with_fr(ctrl.fil.g_noself)


### try to plot with normal plots
#### NB: need to copy and paste into the console, cannot run from here
dev.new(noRStudioGD = T)
svg(filename = 'figures/graph_interactions_ctrl.svg',
    onefile=T)
plot(ctrl.fil.g_noself,
     vertex.label = V(ctrl.fil.g)$name,
     vertex.color = V(ctrl.fil.g)$color,
     edge.color = adjustcolor("black", alpha.f = 0.5),
     edge.width = 2^E(ctrl.fil.g)$log2.o.e,
     layout = custom_layout,
     vertex.label.family = "Arial",
     vertex.label.color = 'black',
     vertex.label.cex = 0.8,
     vertex.size = 25)

leg_incr <- c(2,5,10)

legend("topright",
       legend=as.character(leg_incr),
       col=adjustcolor("black", alpha.f=0.5),
       lwd=c(leg_incr),
       title="Obs/Exp Interactions")

dev.off()


```


### Proportion of each interaction type that occur within hotspots vs other areas

```{r}
# make adjacency matrix of all immune cells
adj_matrices_imms <- lapply(dists, function(d) { 
  tmp <- annot[which(annot$cell_ID %in% rownames(as.matrix(d))), c('cell_ID', 'clust_bcellsubcl')]
  annot_list <- tmp$clust
  names(annot_list) <- tmp$cell_ID
  return(make_adj_mat(d,
                      annot_list,
                      0.1,
                      collapse_query = F)) }) %>%
  bind_rows() %>% 
  ## merge in information about location of the query cells
  merge(.,
        bcell_seurat@meta.data[,c('cell_ID',
                                  'disease',
                                  'context')],
        by.x = 'row.names',
        by.y = 'cell_ID')
  
  ## rename the cell_ID column
  colnames(adj_matrices_imms)[1] <- "cell_ID"
  
  ## replace NA with 0
  adj_matrices_imms <- replace(adj_matrices_imms, is.na(adj_matrices_imms), 0)

# filter for just B.3 cells in LN
# make a dataframe with the number of interactions for each group within each context
cell_types <- colnames(adj_matrices_imms)[2:13]
df <- adj_matrices_imms %>% subset(celltype == 'B.3' & 
                                     disease == 'LN') %>%
  group_by(context) %>%
  summarise(across(all_of(cell_types), sum, .names = "{.col}")) %>%
  t(.) %>% as.data.frame(); colnames(df) <- df[1,]; df <- df[-1,]

# melt the df such that it can be plotte in ggplot2
df$interacting_cell <- row.names(df)
df_plot <- melt(df, id.vars = 'interacting_cell')
df_plot$value <- as.numeric(df_plot$value)
df_plot_props <- df_plot %>% group_by(interacting_cell) %>% summarise(contex = variable,
                                                                      prop_contex = value / sum(value))
df_plot_ns <- df_plot %>% group_by(interacting_cell) %>% summarise(totn = sum(value))


plt <- ggplot() + 
  geom_bar(data = df_plot_props,
           aes(x = interacting_cell, 
               y = prop_contex, 
               fill = contex),
           color = 'black',
           stat = 'identity') +
  geom_text(data = df_plot_ns,
            aes(x = interacting_cell,
                y = 1.05,
                angle = 45,
                label = totn),
            size = 3,
            hjust = 0) +
  scale_fill_manual(values = c('#80b1d3', '#fb8072', '#bebada', '#fdb462')) +
  scale_y_continuous(expand = expand_scale(mult = c(0, 0.12)),
                     breaks = seq(0,1,0.25)) +
  scale_x_discrete(expand = expand_scale(mult = c(0, 0.1))) +
  theme(axis.text.x = element_text(angle = 45, hjust = 1),
        axis.title.y = element_blank()) +
  xlab(label = 'B.3-interacting Cell') +
  labs(fill = "Context")
  
  
ggsave(plt,
       file = 'figures/B3_interactioncontext_SLE.svg',
       width = 5,
       height = 3.5,
       device = svg)

```

